Immunodeficiency, dioxins, stress, and the hormones
免疫缺陷，二恶英（戴奥辛），压力和荷尔蒙
by Raymond Peat
CRITICAL POINTS:
关键点:
*There are many toxins which modify hormonal responses, activating cells and altering the immune system (including estrogens and dioxins.) When these act early in life, extremely small amounts can cause life-long changes.
*有许多毒素会改变荷尔蒙反应，激活细胞，改变免疫系统(包括雌激素和二恶英)。当这些行为在生命早期发生时，极少量就可能导致终生的改变。
*When respiratory energy production is blocked in stimulated cells, the cells are likely to die. (Cortisol, estrogen, polyunsaturated oils have this effect, especially on thymus cells.)
*当受刺激细胞的呼吸能量产生受阻时，细胞很可能死亡。(皮质醇、雌激素、多不饱和油脂都有这种作用，尤其是对胸腺细胞。)
*Antibodies are involved in removing the debris of cells that have disintegrated. Intense cellular damage causes many “autoantibodies” to be produced. People with AIDS have a high incidence of “autoimmunity.”
*抗体参与清除分解后的细胞碎片。强烈的细胞损伤会产生许多“自身抗体”。艾滋病患者“自身免疫”的发病率很高。
*Endogenous retroviruses are activated by toxins known to be associated with immunodeficiency. Everyone has endogenous retroviruses. The antibodies which are used to diagnose “HIV” infection can, in the demonstrated absence of that virus, be produced in connection with lupus, Sjogren's syndrome, and arthritis. These autoimmune conditions are promoted by estrogen.
内源性逆转录病毒被已知与免疫缺陷相关的毒素激活。每个人都有内源性逆转录病毒。用于诊断“HIV”感染的抗体，在证明没有该病毒的情况下，可与狼疮、干燥综合征和关节炎有关。这些自身免疫性疾病是由雌激素引起的。
*Estrogen activates the production of cortisol, and damages the normal feedback control, causing both cortisol and ACTH to be elevated.
*雌激素激活皮质醇的产生，破坏正常的反馈控制，导致皮质醇和促肾上腺皮质激素升高。
*Estrogen causes chronically elevated free fatty acids, and synergizes with unsaturated fats.
*雌激素会导致游离脂肪酸长期升高，并与不饱和脂肪协同作用。
*Estrogen inhibits thyroid function.
*雌激素抑制甲状腺功能。
Hypercortisolism is typically associated with hypothyroidism, and both tend to cause the loss of lean body mass.
高皮质醇症通常与甲状腺功能减退有关，两者都倾向于导致瘦体重的减少。
*AIDS is often compared to Addison's disease, because of hyponatremia (loss of sodium) and fatigue. Hypothyroidism causes hyponatremia and many other features seen in AIDS.
*由于低钠血症(钠的流失)和疲劳，艾滋病经常被比作阿狄森氏病。甲状腺机能减退会导致低钠血症和艾滋病的许多其他特征。
*Increased levels of cortisol, estrogen, and polyunsaturated fatty acids, and decreased levels of the active thyroid hormone (T3) and (placental) progesterone have been found to occur in AIDS.
*研究发现，艾滋病患者皮质醇、雌激素和多不饱和脂肪酸水平升高，活性甲状腺激素(T3)和(胎盘)孕酮水平下降。
*Progesterone can contribute to the inhibition of HIV replication and transmission.
*孕酮有助于抑制艾滋病毒的复制和传播。
*Common environmental factors can produce hormonal changes leading to immunodeficiency.
*常见的环境因素可引起激素变化，导致免疫缺陷。
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One hospital in southern Vietnam admitted 437 septicemia patients between mid-1993 and 1994; 23% of the adults died.
In 8 months, 17,000 seals died of infections in Europe. In California, many seals die with an unusual form of metastatic cancer. Seals are highly contaminated with industrial dioxins.
In Africa, aflatoxin is strongly associated with immunodeficiency. In animals, both dioxin and aflatoxin activate the expression of viruses.
Endometriosis is stimulated by dioxins. Environmental estrogens affect the immune system.
越南南部的一家医院在1993年中期至1994年期间收治了437名败血症患者;23%的成年人死亡。
在8个月内，欧洲有17000只海豹死于感染。在加州，许多海豹死于一种不寻常的转移性癌症。海豹被工业二恶英严重污染。
在非洲，黄曲霉毒素与免疫缺陷密切相关。在动物体内，二恶英和黄曲霉毒素都能激活病毒的表达。二恶英刺激子宫内膜异位症。环境雌激素会影响免疫系统。
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It has been over ten years since I wrote about “AIDS” (e.g., “Repairing the Immune System,” in Cofactors in AIDS and HIV infection, edited by R.R. Watson, l989) and the official doctrine that it is caused by the “HIV” virus still hasn't been supported by anything that resembles real science. Duesberg's arguments have never been answered (except by bureaucratic thuggery).
自从我在1989年R.R. Watson编辑的《艾滋病和HIV感染的辅助因素》一书中写了关于“艾滋病”的文章(如“修复免疫系统”)以来，已经有十多年的时间了，而关于艾滋病是由“HIV”病毒引起的官方学说仍然没有得到任何类似真正科学的支持。杜斯伯格的观点从未得到回应(除了官僚主义的暗杀)。
In 1989 I pointed out that septicemia, blood stream infection, in young adults, which used to be a rare thing, and which indicates defective immunity, has been increasing in a remarkably continuous way since the late 1940s, and I reviewed the many things in our environment that are known to suppress immunity, and which have become increasingly prevalent in ourenvironment–unsaturated vegetable oils, ferrous iron and carrageenan in our foods, lead in air, food, and water, exposure to medical, military, and industrial ionizing radiation, vaccinations, pesticides, chlorinated hydrocarbons, nitric oxide (smog and medications) and oral contraceptives and environmental estrogens, in particular. Of these factors, only radiation and lead exposure have decreased in the last several years, after several decades of rapid increase. The widespread use of diuretics in pregnancy, which began in the 1950s and contributed to an epidemic of premature births, also declined after the late 1960s. Most of these environmental factors damage the thymus gland, which regulates the immune system, and by acting on the thymus their effects tend to be additive with other immunosuppressive factors, including cancer, traumatic injury, inflammation, toxins in spoiled food (e.g., aflatoxins) and malnutrition.
1989年,我指出,败血症,血液感染,在年轻的成年人,它曾经是一个罕见的事情,表明免疫缺陷,值得注意的是连续的方式一直在增加自1940年代末以来,我回顾了很多东西在我们的环境中已知的抑制免疫力,它们在我们的环境中变得越来越普遍——不饱和植物油，食物中的亚铁和卡拉胶，空气，食物和水中的铅，接触医疗，军事和工业电离辐射，疫苗，杀虫剂，氯代烃，特别是一氧化氮(烟雾和药物)和口服避孕药和环境雌激素。在这些因素中，只有辐射和铅暴露在几十年的快速增加之后，在过去几年中有所减少。20世纪50年代开始在怀孕期间广泛使用利尿剂，这导致了早产的流行，60年代后期之后也有所减少。这些环境因素大多会损害调节免疫系统的胸腺，通过作用于胸腺，它们的影响往往会与其他免疫抑制因素叠加，包括癌症、创伤、炎症、变质食物中的毒素(如黄曲霉毒素)和营养不良。
Cancer, AIDS, and extreme hypothyroidism have several features in common–they cause tissue loss and organ damage, with immunodeficiency and intense activation of the stress hormones, including cortisol. In cancer and AIDS, a good case has been made for the primacy of stress-induced wasting as the main cause of death. Whatever one might believe to be the cause of cancer and AIDS, it is always good for the patient to prevent tissue damage from the stress associated with the sickness. Since the stress hormones primarily destroy tissues by the activation of specific proteases, the use of protease inhibitors for treating AIDS could conceivably be affecting the stress response. However, the body's normal protection against the cortisol-activated proteases is centered on the protective hormones, progesterone, thyroid, and the androgens.
癌症、艾滋病和极端甲状腺功能减退症有几个共同特征——它们会导致组织损失和器官损伤，伴有免疫缺陷和应激激素(包括皮质醇)的强烈激活。在癌症和艾滋病中，压力引起的消瘦是死亡的主要原因，这是一个很好的例子。无论人们认为癌症和艾滋病的病因是什么，对病人来说，防止与疾病相关的压力造成的组织损伤总是有好处的。由于应激激素主要通过激活特定的蛋白酶来破坏组织，使用蛋白酶抑制剂治疗艾滋病可能会影响应激反应。然而，身体对皮质醇激活的蛋白酶的正常保护主要集中在保护激素、孕酮、甲状腺和雄激素上。
Environmental stress
环境压力
One of the most broadly substantiated principles in biology is that a great variety of harmful causes all lead to a few forms of biological harm–the concept of the stress reaction shows the powerful implications of the principle. Stress, no matter what the specific cause, has a particularly destructive effect on three organ systems: The nervous system, the immune system, and the reproductive system. Inflammation, lipid peroxidation, tissue atrophy, the “calcium catastrophe” (when almost anything goes wrong, calcium can transmit and amplify and extend the problem, but isn't itself the source of the problem), mitochondrial decay, and similar events help to define the stress reaction in greater detail.
Hans Selye showed that the thymus shrinks very early in the stress reaction. In his understanding of the process, when adaptation was followed by the “exhaustion phase,” the adrenal glands had simply become exhausted from overuse. F. Z. Meerson's work showed that cortisol, and the free fatty acids mobilized by stress, have a toxic influence on the mitochondrial energy production system. Both cortisol and the free fatty acids block the efficient use of glucose for producing energy, creating a diabetes-like condition. The exhaustion problem caused by excessive stress is generalized, not just a matter of adrenal insufficiency.
Meerson's work created the basis for undersanding several degenerative processes, especially the phenomenon of “excitotoxicity,” in which the combination of excessive stimulation and deficient energy supply damages or kills cells.
生物学中得到最广泛证实的原则之一是，各种各样的有害原因都会导致几种形式的生物伤害——应激反应的概念显示了这一原则的强大含义。压力，无论具体原因是什么，对三个器官系统都有特别破坏性的影响:神经系统、免疫系统和生殖系统。炎症、脂质过氧化、组织萎缩、“钙灾难”(当几乎任何事情出错时，钙可以传播、放大和扩大问题，但它本身不是问题的根源)、线粒体衰退，以及类似的事件有助于更详细地定义应激反应。
Hans Selye证明胸腺在应激反应的早期就萎缩了。在他的理解中，当适应之后是“疲惫阶段”时，肾上腺只是因为过度使用而变得疲惫。F. Z. Meerson的研究表明，皮质醇和应激激活的游离脂肪酸对线粒体能量生产系统有毒性影响。皮质醇和游离脂肪酸都阻碍了葡萄糖的有效利用以产生能量，造成了类似糖尿病的状况。由过度压力引起的疲惫问题是普遍的，而不仅仅是肾上腺功能不全的问题。
Meerson的工作为理解一些退化过程，特别是“兴奋毒性”现象奠定了基础，在这种现象中，过度刺激和缺乏能量供应的结合会损害或杀死细胞。
Selye believed that some hormones are antagonistic to each other. A few of the oppositions that he identified have been thoroughly researched, especially the catabolic/anabolic functions of glucocorticoids and androgens, and the shock/antishock functions of estrogen and progesterone, respectively.
Puberty, because of hormonal changes, especially increased estrogen, can be seen as the first stage of a chronic stress, resembling diabetes, since elevated free fatty acids cause “insulin resistance,” with slightly impaired oxidation of glucose. The thymus shrinks considerably at puberty, under the influence of the hormonal changes and the increased free fatty acids (caused mainly by estrogen). The degenerative diseases can be seen as the cumulative result of stress, in which tissue damage results from the diabetes-like impairment of energy production.
Selye认为有些激素是相互拮抗的。他发现的一些反对意见已经得到了充分的研究，特别是糖皮质激素和雄激素的分解/合成代谢功能，以及雌激素和孕酮的休克/抗休克功能。
青春期，由于荷尔蒙的变化，特别是雌激素的增加，可以被看作是慢性应激的第一阶段，类似于糖尿病，因为游离脂肪酸的升高导致“胰岛素抵抗”，葡萄糖的氧化轻微受损。在荷尔蒙变化和游离脂肪酸增加(主要由雌激素引起)的影响下，胸腺在青春期大幅萎缩。退行性疾病可以被视为压力的累积结果，其中组织损伤是由类似糖尿病的能量生产障碍引起的。
The thymus, and the thymus-dependent areas of the spleen, are required for full and subtle control of immunity. In the absence of thymic control, the B cells are still able to produce antibodies, but they are more likely to produce autoantibodies.
胸腺和脾脏中依赖胸腺的区域对免疫的全面和微妙的控制是必需的。在没有胸腺控制的情况下，B细胞仍然能够产生抗体，但它们更有可能产生自身抗体。
Stress produces a variety of cellular changes, including the production of the “shock proteins.” These proteins can make up 20% of the cell's total protein content. In themselves, the shock proteins are immunosuppressive. They can be recognized by the immune system as antigens, and so are a factor in the appearance of “autoimmune” antibodies. The autoantibodies themselves are often blamed for the diseases they are sometimes associated with, but since they can be present (for example, following removal of the spleen) in people who have no symptoms, their function is probably to facilitate the removal of tissues which are defective for some other reason. The shock proteins could be one of the signals that activate the immune system to remove damaged tissue, and they might be involved in the removal of senescent cells, though I don't think any experiments have been done to test this idea.
压力会产生各种各样的细胞变化，包括“休克蛋白”的产生。这些蛋白质可占细胞总蛋白质含量的20%。休克蛋白本身具有免疫抑制作用。它们可以被免疫系统识别为抗原，因此也是“自身免疫”抗体出现的一个因素。自身抗体本身往往归咎于他们有时相关的疾病,但由于他们可以存在(例如,切除脾脏后)的人没有任何症状,其功能可能是为了便于清除有缺陷的组织一些其他原因。休克蛋白可能是激活免疫系统移除受损组织的信号之一，它们可能参与了衰老细胞的移除，尽管我不认为有任何实验可以验证这一观点。
Besides activating the cells to produce massive amounts of the shock proteins, stress can also activate the so-called hormone receptors, such as estrogen receptors, even in the absence of the hormones. Stress also activates the endonucleases, which cut sections out of the DNA molecules, and activates mobile genetic elements, producing genetic instability. Like cortisol and estrogen, stress itself activates integrated retroviruses. The “endogenous retroviruses” make up nearly 10% of the human genome, and many of them locate themselves in regulatory sites in the chromosomes.
除了激活细胞产生大量的休克蛋白外，压力还可以激活所谓的激素受体，如雌激素受体，即使在激素缺乏的情况下。压力还会激活内切酶，将DNA分子切出一部分，并激活可移动的遗传元素，产生遗传不稳定性。就像皮质醇和雌激素一样，压力本身会激活整合逆转录病毒。“内源性逆转录病毒”占人类基因组的近10%，其中许多病毒位于染色体的调控位点。
Since stress lowers the discriminatory ability of the immune system, and stimulates the expression of retroviruses, the antibodies sometimes seen in association with immunodeficiency may be similar to the various autoantibodies that are also produced by stress.
由于应激降低了免疫系统的识别能力，并刺激逆转录病毒的表达，有时与免疫缺陷相关的抗体可能与应激产生的各种自身抗体相似。
People who have autoimmune diseases such as lupus and Sjogrens syndrome (which are promoted by estrogen: Ahmed and Talal) have antibodies which sometimes react positively in the AIDS test, and searches for the HIV virus in such people have found no evidence of it. (Nelson, et al., 1994; Deas, et al., 1998.) Treatments for roundworms and other parasites cause antibodies to retroviruses to appear in animals that previously tested negative; this might account for the high rates of positive tests for HIV in areas such as Africa in which treatment for filiariasis is common (Kitchen and Cotter, 1988).
患有自身免疫性疾病的人，如狼疮和干燥综合征(由雌激素促进:艾哈迈德和塔拉勒)，有时在艾滋病测试中有抗体反应积极，在这些人身上寻找艾滋病毒没有发现证据。(Nelson等人，1994;Deas等，1998。)对蛔虫和其他寄生虫的治疗会导致此前检测呈阴性的动物出现逆转录病毒抗体;这可能解释了在非洲等治疗丝虫病很常见的地区HIV阳性检测率高的原因(Kitchen and Cotter, 1988)。
Organisms are most sensitive to environmental damage early in life, especially prenatally. This is the period in which normal hormone exposure masculinizes the brain, for example. The term “imprinting” refers to the extreme responsiveness of the organism at this time, and it has been extended to include long lasting influences which may result from abnormally high or low levels of natural substances, or from the presence of other, abnormal substances during the sensitive period. The effects of early “imprinting” can cause permanently altered sensitivities. In animal studies, L. C. Strong showed that prenatal influences determine the age at which puberty and reproductive senescence occur. In humans, premature birth, a powerful stressor, is associated with premature puberty. The thymus is damaged both by premature birth and by puberty. The effects of damage early in life will increase vulnerability in subsequent decades.
生物在生命早期对环境损害最为敏感，尤其是在产前。例如，在这个时期，正常的荷尔蒙暴露会使大脑男性化。“印迹”一词是指生物体此时的极度反应能力，它已被扩展到包括自然物质异常高或低水平，或在敏感时期存在其他异常物质可能造成的长期影响。早期“印记”的影响可能导致永久性的敏感性改变。在动物研究中，l.c.斯特朗(l.c. Strong)表明，产前影响决定了青春期和生殖衰老发生的年龄。对人类来说，早产是一种强大的压力源，与青春期提前有关。胸腺会因早产和青春期而受损。生命早期受到损害的影响将在随后几十年增加脆弱性。
When babies are imprinted by the mother's disturbed hormones, or by diuretics, by milk substitutes, or by industrial effluents, the worst effects are likely to be seen decades later, or even generations later. A similar long-range effect can be produced by nutritional deficiencies.
当婴儿被母亲紊乱的荷尔蒙、利尿剂、牛奶替代品或工业废水所影响时，最糟糕的影响可能会在几十年后，甚至几代人之后出现。营养缺乏也会产生类似的长期影响。
Although more mature organisms are less sensitive to stress, both early imprinting, and the cumulative effects of exposure, will cause some individuals to be much more sensitive than others, and aging itself increases vulnerability.
虽然较成熟的生物体对压力的敏感性较低，但无论是早期印记，还是暴露的累积效应，都会导致一些个体比其他个体更加敏感，而衰老本身也增加了脆弱性。
If the present epidemic of immunodeficiency is produced by environmental stress, then we should expect to see a variety of other stress-related diseases increasing at roughly the same time. When a stressor is acting through imprinting, then the harmful effects may not be seen until 20 or 30 years later, but when the stressor has acute and immediate effects, the effects should rise and fall at roughly the same time as the environmental cause.
如果目前免疫缺陷的流行是由环境压力造成的，那么我们应该可以预期，各种其他与压力相关的疾病大致会在同一时间增加。当压力源通过印记作用时，其有害影响可能要到20或30年后才会显现出来，但当压力源具有急性和即时的影响时，其影响应该与环境原因大致同时上升和下降。
The rise of the Acquired Immunodeficiency Syndrome during the last 50 years hasn't been the only health problem that has grown rapidly during that time. The “flesh eating bacteria,” causing necrotizing fasciitis and related conditions, should probably be classed along with septicemia/bacteremia as the consequence of a weakened immune system, but there are many other diseases that have followed a similar pattern, which might be caused by the same factors which are causing immunodeficiency. Thyroid diseases (mostly in women), some autoimmune diseases including primary biliary cirrhosis (mostly in women) and inflammatory bowel disease, liver cancer, diabetes (doubling in children since 1949), prostate cancer, decreased sperm counts, premature births and birth defects, minimal brain dysfunction-attention deficit-hyperactivity, cerebral palsy, premature puberty (which is associated with premature birth), congestive heart failure, osteoporosis (independently of the changing age-structure of the population), depression (most common in women, more than doubling among children in recent decades), and multiple sclerosis have increased in prevalence during this period. Some of these conditions are strongly associated with each other, for example, primary biliary cirrhosis, breast cancer, and osteoporosis.
在过去的50年里，获得性免疫缺陷综合症的上升并不是唯一一个在这段时间里迅速增长的健康问题。“食肉细菌”,导致坏死性筋膜炎和相关条件,应该分类以及败血症、菌血症的结果削弱了免疫系统,但也有许多其他疾病,也出现了类似的状况,这可能是由于相同的因素,导致免疫缺陷。甲状腺疾病(主要发生在妇女身上)、一些自身免疫性疾病，包括原发性胆汁性肝硬化(主要发生在妇女身上)、炎症性肠病、肝癌、糖尿病(自1949年以来儿童人数增加了一倍)、前列腺癌、精子数量减少、早产和出生缺陷、轻微的脑功能障碍-注意缺陷-多动症、脑瘫、青春期提前(与早产有关)、充血性心力衰竭、骨质疏松症(与人口年龄结构的变化无关)、抑郁症(在妇女中最常见，近几十年儿童中增加了一倍多)和多发性硬化症在这一时期的患病率增加。其中一些疾病是相互关联的，例如原发性胆汁性肝硬化、乳腺癌和骨质疏松症。
It is common knowledge, among people who study immunity, that radiation, polyunsaturated fatty acids, estrogens, and dioxins are toxic to the thymus gland, and can produce immuno-deficiency. They mimic or accelerate the thymic atrophy of aging, causing a deficient thymus-dependent immune response, usually without harming the ability of B cells to produce antibodies. There are probably many examples of damage to immune systems, besides immunodeficiency, caused by these agents. Slight damage to the immune system, such as can be produced by hypoglycemia or other energy deficit–creates an exaggerated inflammatory response, and the release of the mediators of inflammation, including histamine, serotonin, and prostaglandins, activates the stress hormone system, leading to further biological damage. Liver disease and several other “autoimmune” diseases involve abnormal immune responses, probably including thymic deficiency and an intensified inflammatory response. The fact that livers transplanted from female donors to male recipients are less successful than are livers from male donor transplanted into female recipients, is consistent with the idea that autoantibodies (which are far more common in women than in men) are a relatively harmless response to changes in the organs themselves.
研究免疫的人都知道，辐射、多不饱和脂肪酸、雌激素和二恶英对胸腺是有毒的，会导致免疫缺陷。它们模仿或加速衰老引起的胸腺萎缩，导致依赖胸腺的免疫反应不足，通常不会损害B细胞产生抗体的能力。除了免疫缺陷外，可能还有许多由这些因子引起的免疫系统损害的例子。轻微的免疫系统损伤，比如低血糖或其他能量不足，就会产生过度的炎症反应，而炎症介质的释放，包括组胺、血清素和前列腺素，就会激活应激激素系统，导致进一步的生物损伤。肝病和其他几种“自身免疫”疾病涉及异常的免疫反应，可能包括胸腺缺乏和炎症反应加剧。这一事实从女性捐赠者男性接受肝脏移植的成功比从男性捐献移植到女性接受者,肝脏是一致的想法,自身抗体(女性比男性更常见)是一种相对无害的应对器官本身的变化。
Are antiviral therapies working? Ivan Ilich, in Medical Nemesis, showed that historically, many diseases have had characteristic incidence curves, rising to a maximum, and then falling away to relative insignificance, independently of what people were doing as treatment or prevention. As susceptible people are exposed to conditions that cause a disease, they will get sick, and then either die or develop resistance. The conditions which at first caused increasing disease incidence, will eventually tend to affect only children who haven't developed resistance.
抗病毒治疗有效吗?伊凡·伊里奇在《医学复仇》中指出，历史上，许多疾病都有其特有的发病率曲线，上升到最大值，然后下降到相对不显著，这与人们的治疗或预防措施无关。当易感人群暴露在导致疾病的环境中，他们就会生病，然后要么死亡，要么产生抗药性。最初导致疾病发病率上升的条件，最终将倾向于影响尚未产生抵抗力的独生子女。
If AIDS mortality rose rapidly to a peak a few years ago, and then began falling, we should ask whether this pattern fits that of other diseases discussed by Ilich. Looking for causes other than the virus, we might find a parallel in the rise and fall of some other factor.
In the 1950s, new diuretics came on the market, and millions of pregnant women took them. It was predicted that there would be an epidemic of brain damage as a result, and in fact the incidence of hyperactivity, attention-deficit, and other “minimal” brain damage disorders did rise during those years. After about 15-20 years, experiences such as the Thalidomide episode caused physicians to temper their enthusiasm for the use of drugs during pregnancy. The incidence of low birth-weight babies in the U.S. peaked around 1965, and 28 years later AIDS mortality in the US peaked. The rising curve had followed both the increase in radioactive fallout from atmospheric testing of large numbers of atomic bombs up to 1963, and the intense promotion of the new diuretics beginning in the early 1950s. The peak in AIDS mortality in 1993 came ten or twelve years after the long decline in SAT scores had stopped. (The most extreme declines in SAT scores had occurred among the brightest students, disproving the contention that the average score fell simply because more students were taking the tests.) The same prenatal damage which caused the extreme decline in SAT scores 18 years later (when the damaged babies reached that age) would have left many of the same individuals with weakened immune systems, which would fail prematurely, but at varying intervals, depending on the exposure to other factors.
如果艾滋病死亡率在几年前迅速上升到一个峰值，然后开始下降，我们应该问，这种模式是否符合伊里奇讨论的其他疾病。寻找病毒之外的原因，我们可能会发现其他一些因素的涨落。
在20世纪50年代，新的利尿剂出现在市场上，数百万孕妇服用了它们。据预测，这将导致脑损伤的流行，而事实上，多动症、注意力缺陷和其他“最小”脑损伤障碍的发病率在那些年确实上升了。大约15-20年后，萨力多胺发作等经历使医生对在怀孕期间使用药物的热情有所降温。美国低出生体重婴儿的发生率在1965年左右达到顶峰，28年后美国艾滋病死亡率达到顶峰。上升曲线是随着1963年之前大量原子弹在大气中试验所产生的放射性沉降物的增加，以及从20世纪50年代初开始新型利尿剂的大力推广而产生的。1993年，在SAT成绩长期下降的趋势停止后的10年或12年，艾滋病死亡率达到了顶峰。(SAT成绩降幅最大的是最聪明的学生，这推翻了平均分下降仅仅是因为更多学生参加考试的观点。)同样的产前损伤导致了18年后(受损婴儿达到那个年龄)SAT分数的极度下降，也会使许多同样的个体的免疫系统变弱，这将会过早地失败，但时间间隔不同，取决于暴露在其他因素中的时间间隔。
The use of unleaded gasoline increased into the 1990s, and there was a corresponding decrease in tissue lead content, reflecting the smaller amount of lead being put into the environment. According to some reports, medical and dental x-ray exposures were declining during this period. Yet other factors, including dioxins and unsaturated dietary fats, were probably increasing.
Although the new protease inhibitors wouldn't be used until years after the AIDS mortality had begun falling, the government and drug companies are claiming that it is the drugs which are decreasing the mortality.
20世纪90年代无铅汽油使用量增加，组织铅含量相应下降，反映出向环境中排放的铅量减少。根据一些报告，在此期间，医疗和牙科x光照射减少。然而，包括二恶英和不饱和饮食脂肪在内的其他因素可能也在增加。
虽然新的蛋白酶抑制剂要到艾滋病死亡率开始下降数年后才会使用，政府和制药公司都声称是药物降低了死亡率。
A Synthesis
综合来看
Many things in our environment are increasing the incidence of certain kinds of liver disease. The liver processes things that are ingested or that enter the blood stream after being inhaled or absorbed through the skin, so in a toxic environment it is susceptible to injury. If deprived of good nutrition or adequate thyroid hormone it is especially sensitive to toxins. The body's own estrogen is a burden on the liver, causing women's livers to be on average slower than men's in processing enviornmental chemicals.
我们环境中的许多因素都在增加某些肝病的发病率。肝脏处理被摄入的东西或通过皮肤吸入或吸收后进入血液的东西，所以在有毒的环境中它很容易受伤。如果缺乏良好的营养或足够的甲状腺激素，它对毒素特别敏感。身体自身的雌激素对肝脏是一种负担，导致女性的肝脏处理环境化学物质的速度平均比男性慢。
Almost any kind of toxin causes the liver to be less efficient at excreting other substances, including hormones. In malnutrition, sickness, and in aging, there is a tendency for higher levels of estrogen to remain circulating in the blood.
几乎任何一种毒素都会导致肝脏分泌其他物质(包括激素)的效率降低。在营养不良、疾病和衰老的情况下，血液中循环的雌激素水平有升高的趋势。
Natural estrogen, and environmental substances that act like estrogen, act as excitants in many types of cell, and at the same time, reduce the efficiency of energy production. Both of these properties relate to its known ability to activate the adrenal glands. A. L. Soderwall, who was my thesis adviser at the University of Oregon, found that estrogen caused hamsters' adrenal glands to enlarge, and that larger doses overstimulated the glands sufficiently to cause tissue damage. It is now known that estrogen acts directly on the adrenal cells to stimulate cortisol production, and that it also stimulates the pituitary to produce more adrenocorticotropin (ACTH), which also stimulates the adrenals; estrogen's effect is to impair the negative feedback, in which cortisol normally shuts down ACTH production. This impaired feedback is characteristic of aging.
天然的雌性激素和像雌性激素一样作用的环境物质，在许多类型的细胞中起到兴奋剂的作用，同时，降低能量生产的效率。这两种特性都与它已知的激活肾上腺的能力有关。A. L. Soderwall，我在俄勒冈大学的论文导师，发现雌激素会导致仓鼠的肾上腺增大，而大剂量的雌激素会过度刺激腺体，导致组织损伤。现在我们知道，雌激素直接作用于肾上腺细胞以刺激皮质醇的产生，它也刺激垂体产生更多的促肾上腺皮质激素(ACTH)，这也刺激肾上腺;雌激素的作用是削弱负反馈，在这种负反馈中，皮质醇通常会关闭促肾上腺皮质激素的产生。这种受损的反馈是衰老的特征。
Estrogen directly causes the thymus gland to atrophy, and several of its effects, such as increased adrenal activity and elevated free fatty acids, also contribute to the shrinkage of the thymus and the inhibition of its functions. While this is happening, the B cells, which normally are under the control of the thymus cells, are not killed by estrogen, and actually seem to be stimulated by estrogen to produce certain types of antibodies. This combination of effects, weakening the thymus and stimulating antibody production, is thought to contribute to the development of autoimmune diseases. Estrogen also stimulates mast cells and similar cells to release histamine and other promoters of inflammation, and these effects are probably closer to the actual problem in the autoimmune diseases. Several of the substances formed under the influence of estrogen interfere with energy production and contribute to cellular excitation, causing tissue injury.
雌激素直接导致胸腺萎缩，它的一些作用，如肾上腺活性的增加和游离脂肪酸的升高，也有助于胸腺的收缩和抑制其功能。当这种情况发生时，通常在胸腺细胞控制下的B细胞，并没有被雌激素杀死，实际上似乎是被雌激素刺激产生某些类型的抗体。这种削弱胸腺和刺激抗体产生的综合效应被认为是自身免疫性疾病的发展原因之一。雌激素还刺激肥大细胞和类似细胞释放组胺和其他炎症促进因子，这些作用可能更接近自身免疫性疾病的实际问题。在雌激素的影响下形成的一些物质干扰能量的产生并促进细胞兴奋，导致组织损伤。
Cortisol also stimulates antibody production while suppressing thymic immunity (Norbiato, et al., 1997).
Estrogen and stress cause increased levels of free fatty acids to circulate. The polyunsaturated fatty acids are immunosuppressive, antithyroid, diabetogenic, inhibit respiration, and promote the actions of estrogen and cortisol.
皮质醇也刺激抗体的产生，同时抑制胸腺免疫(Norbiato等，1997)。
雌激素和压力导致血液循环中的游离脂肪酸水平增加。多不饱和脂肪酸具有免疫抑制、抗甲状腺、糖尿病、抑制呼吸和促进雌激素和皮质醇的作用。
People suffering from AIDS have been found to have increased estrogen, with high cortisol and ACTH, and very low T3. (Unfortunately, some researchers and the editors who publish their ideas, conclude that the hormones don't cause the stress and wasting symtpoms, because they call thyroid a “catabolic hormone,” and because they describe the fatigue and sodium deficiency as evidence of “deficiency of cortisol.” Such is the state of the research establishment.)
研究发现，艾滋病患者体内雌激素水平升高，皮质醇和ACTH水平较高，T3水平很低。(不幸的是，一些发表他们观点的研究人员和编辑得出的结论是，这些激素不会导致压力和消瘦症状，因为他们把甲状腺称为“分解代谢激素”，还因为他们把疲劳和缺钠描述为“皮质醇缺乏”的证据。这就是研究机构的现状。)
In animal experiments, and a few human tests, the HIV and similar viruses have produced effects that could plausibly explain some of the conditions seen in AIDS, such as damage to brain cells (C. Pert, R. Sapolsky), and altered steroid secretion. But this is real science, that promises to link up with information about stress, aging, allergy, and biological adaptability.
在动物实验和一些人体试验中，艾滋病毒和类似病毒产生的效果似乎可以解释在艾滋病中看到的一些情况，如脑细胞损伤(C. Pert, R. Sapolsky)和类固醇分泌改变。但这是真正的科学，它承诺将与压力、衰老、过敏和生物适应性相关的信息联系起来。
For example, Sapolsky's group (Brooke, et al., 1998) found that the nerve toxicity caused by a viral protein (called gp120) synergizes with glucocorticoid toxicity, lowering the ATP level and inhibiting mitochondrial function, and that simply supplying the nerve with additional energy protects it from destruction. In other words, the viral peptide just increases excitotoxicity.
Another group (Amirhessami-Aghili and Spector, 1991) found that the presence of the virus can decrease the production of progesterone. Since progesterone blocks (Lee, et al., 1997) the expression (and transmission) of the virus, this suggests how the overgrowth of the virus might be triggered by stress–once progesterone synthesis falls, a vicious circle could get started.
例如，Sapolsky的小组(Brooke等人，1998年)发现由病毒蛋白(称为gp120)引起的神经毒性与糖皮质激素毒性协同作用，降低ATP水平并抑制线粒体功能，而仅仅是为神经提供额外的能量就可以保护它免受破坏。换句话说，病毒肽只是增加了兴奋性毒性。
另一组(Amirhessami-Aghili和Spector, 1991)发现，病毒的存在可以减少孕酮的产生。由于孕酮阻碍了病毒的表达(和传播)，这表明压力可能会引发病毒的过度生长——一旦孕酮合成下降，一个恶性循环就可能开始。
Lee, et al., found that progesterone can help to prevent transmission of the virus from an infected mother to the fetus. But the most interesting study of the virus in pregnancy involved mice that were engineered to contain extremely large quantities of the HIV provirus (De, et al., 1997). At birth, they seemed normal, but within a few days their skin became diseased, and they quickly wasted away and died. The experimenters realized that something present in the mother's body had permitted normal development up to the point of birth, and then the wasting disease set in. The placental hormone, chorionic gonadotropin, is produced in large amounts during pregnancy. The experimenters gave newborn infected mice regular doses of human chorionic gonadotropin (hCG), and they developed normally.
Lee等人发现孕激素可以帮助防止病毒从受感染的母亲传播给胎儿。但是，对妊娠期病毒的最有趣的研究涉及到被改造成含有大量艾滋病毒原病毒的老鼠(De, et al.， 1997)。出生时，它们看起来很正常，但没过几天，它们的皮肤就发生了病变，很快就消瘦下去并死去了。实验人员意识到，母亲体内的某种物质一直到出生时都允许其正常发育，然后就患上了消耗性疾病。胎盘激素，绒毛膜促性腺激素，在怀孕期间大量产生。实验人员给被感染的新生小鼠定期注射人绒毛膜促性腺激素(hCG)，它们发育正常。
Rodents don't respond to gonadotropins or other ovarian stimulation exactly the way pigs and primates and people do. For example, prolactin and melatonin usually inhibit progesterone synthesis in people, but in rodents, they increase it. So it's necessary to see exactly what happens to the ovarian hormones when a mouse is given hCG. In 1996, another group (H. Krzanowska and M. Szoltys) had done that, and found that hCG greatly increases progesterone synthesis, but decreases estrogen.
啮齿动物对促性腺激素或其他卵巢刺激的反应并不像猪、灵长类动物和人那样。例如，催乳素和褪黑素通常会抑制人体内孕酮的合成，但在啮齿动物体内，它们会增加孕酮的合成。所以有必要看看当给老鼠注射hCG时，卵巢激素会发生什么变化。1996年，另一组研究人员(H. Krzanowska和M. Szoltys)也这样做了，他们发现hCG大大增加了孕酮的合成，但降低了雌激素。
Considering the progesterone-HIV experiments together, I am reminded of a science fiction movie, in which a disease from another planet killed everyone in the lab that was studying it, except for one woman, who turned out to be pregnant.
想到孕酮- hiv实验，我想起了一部科幻电影，在电影中，来自另一个星球的一种疾病杀死了研究它的实验室里的所有人，除了一名妇女，她后来怀孕了。
The medical version of AIDS research, though, pushes aside all of the real science, in favor of a simplistic idea that the virus kills the cells of the immune system, and uses false diagnostic methods and deadly drugs to treat something which too often doesn't exist, while denying that there are other real causes of immune deficiency and wasting-sickness, etc.
然而，艾滋病研究的医学版本抛开了所有真正的科学，支持一种简单的观点，即病毒会杀死免疫系统的细胞，并使用错误的诊断方法和致命的药物来治疗一些通常并不存在的东西，同时否认造成免疫缺陷和消瘦症等的其他真正原因。
Aging is characterized by loss of lean body mass, immunodeficiency, and a variety of autoimmune reactions. My perennial argument has been that decreased thyroid and progesterone, associated with increased estrogen and stress hormones, are largely responsible for those changes. The huge investment in AIDS research has found that these occur in AIDS, but, because of the medical pharmaceutical culture which has created myths about these hormones, no one is yet interpreting the hormone imbalances in ways that would reveal their responsibility for the symptoms. While the institutionalized theory claims that the HIV virus is responsible for the syndrome, the hormones are reduced to epiphenomena.
衰老的特征是瘦体重的减少，免疫缺陷和各种自身免疫反应。我一直认为，甲状腺和黄体酮的减少，与雌激素和应激激素的增加有关，是这些变化的主要原因。对艾滋病研究的巨额投资已经发现，这些激素在艾滋病中也存在，但是，由于医药文化对这些激素产生了误解，还没有人对激素失衡的解释能够揭示它们对这些症状的责任。虽然制度化的理论声称，艾滋病毒是导致综合症的原因，但激素被降低为偶发现象。
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J Neuroimmunol 1998 Dec 1;92(1-2):133-8 An inhibitor of inducible nitric oxide synthase ameliorates experimental autoimmune myocarditis in Lewis rats. Shin T, Tanuma N, Kim S, Jin J, Moon C, Kim K, Kohyama K, Matsumoto Y, Hyun B. We studied the effect of nitric oxide (NO) on experimental autoimmune myocarditis (EAC) in rats. These results suggest that iNOS is upregulated in EAC lesions and increased NO production plays an important role in the development of EAC. In addition, selective iNOS inhibitors may have a therapeutic role in treating certain autoimmune diseases including EAC.
Langenbecks Arch Chir Suppl Kongressbd 1997;114:508-12 [Necrotizing fasciitis]. Billing A, Arendt RM, Arnoldt H, Schildberg FW Necrotizing fasciitis has changed considerably over time.
Clin Infect Dis 1998 Mar;26(3):584-9 Invasive group A streptococcal disease in Taiwan is not associated with the presence of streptococcal pyrogenic exotoxin genes. Hsueh PR, Wu JJ, Tsai PJ, Liu JW, Chuang YC, Luh KT. High-level protease activity and the M1 serotype of the isolates were significantly associated with the clinical signs of STSS and with mortality. M1 serotype and protease activity, as well as host immune status, might play significant roles in the pathogenesis of invasive GAS disease in Taiwan.
Can J Surg 1997 Feb;40(1):18-25 Group A Streptococcus invasive infections: a review. Weiss KA, Laverdiere M. The incidence of group A Streptococcus (GAS) invasive infections has been increasing worldwide,and there is no obvious explanation for this phenomenon.
Unfallchirurg 1993 Apr;96(4):181-91 [Necrotizing soft tissue infections]. [Article in German] Kach K, Kossmann T, Trentz O. Necrotizing soft tissue infections are a group of life- and limb-threatening infections. They are caused by aerobic and anaerobic bacteria occasionally in a synergistic polymicrobial combination. The literature describing necrotizing soft tissue infections is controversial and often contradictory.
Ann Dermatol Venereol 1993;120(6-7):469-72 [Epidemiology and etiopathogeny of necrotizing fasciitis and streptococcal shock syndrome]. Simonart T, Simonart JM, Schoutens C, Ledoux M, De Dobbeleer G. A significant increase in the frequency of necrotizing fasciitis caused by streptococci of group A has recently been noted. The disease usually appears in individuals without obvious risk factors. The sensitivity of the host is linked to the genetic expression of the V. beta. elements on the surface of lymphocytes.
J Infect 1989 May;18(3):231-48 Invasive streptococcal infections in the era before the acquired immune deficiency syndrome: a 10 years' compilation of patients with streptococcal bacteraemia in North Yorkshire. Barnham M. Significant streptococcal (non-pneumococcal, non-enterococcal) bacteraemia was detected in 100 patients in two Health Districts of North Yorkshire in the decade 1978-1988.
Transpl Immunol 1998 Jun;6(2):84-93 Stress protein-induced immunosuppression: inhibition of cellular immune effector functions following overexpression of haem oxygenase (HSP 32). Woo J, Iyer S, Cornejo MC, Mori N, Gao L, Sipos I, Maines M, Buelow R. The results indicate that overexpression of HO results in the inhibition of several immune effector functions and thus provides an explanation for stress-induced immunosuppression.
Genome 1998 Oct;41(5):662-8. A single-primer PCR-based retroviral-related DNA polymorphism shared by two distinct human populations. Deb P, Klempan TA, O'Reilly RL, Singh SM Department of Zoology, University of Western Ontario, London, Canada. “Almost 10% of the human genome consists of DNA sequences that share homology with retroviruses.These sequences, which represent a stable component of the human genome (although some may retain the ability to transpose), remain poorly understood.” “Such novel polymorphisms should provide useful markers and permit assessment of evolutionary mechanisms associated with retroviral-related genomic evolution. ”
Gen Pharmacol 1998 May;30(5):685-7, Imprinting of thymic glucocorticoid receptor and uterine estrogen receptor by a synthetic steroid hormone at different times after birth. Csaba G, Inczefi-Gonda A.
J Clin Endocrinol Metab 1998 Dec;83(12):4373-81. Human immunodeficiency virus induction of corticotropin in lymphoid cells. Hashemi FB, Hughes TK, Smith EM.
Eur J Cancer Clin Oncol 1988 Jul;24(7):1179-83. Abnormal free fatty acids and cortisol concentrations in the serum of AIDS patients.Christeff N, Michon C, Goertz G, Hassid J, Matheron S, Girard PM, Coulaud JP, Nunez EA. The serum free fatty acid (FFA), cortisol and urinary creatinine, 17-hydzoxycorticosteroid and 17-oxosteroid concentrations of acquired immunedeficiency syndrome (AIDS-I: beginning and AIDS-II: end phase) and AIDS-related complex (ARC) patients were determined. Both groups were compared to a control group (healthy men). ARC and AIDS-I patients. The ratios of stearic (C18:0) to oleic (C18:1) acid were 75%, P less than 0.01 (ARC) and 45%, P less than 0.05 (AIDS-I) greater than normal, due to a decrease in the relative percentage of monounsaturated fatty acids by 25%, P less than 0.001 (ARC) and 20%, P less than 0.01 (AIDS-I). In contrast, the relative percentage of polyunsaturated fatty acids was 85% greater than normal (P less than 0.001) in ARC and 100% greater than normal (P less than 0.001) in AIDS-I patients. Total FFA levels did not differ from controls. Serum cortisol levels were 35% (P less than 0.01) above normal in ARC and 60% (P less than 0.001) above normal in AIDS-I patients. Urinary 17-hydroxycorticosteroids and 17-oxosteroids were very low (2-3-fold lower than normal values, P less than 0.001) in both groups of patients. Urinary creatinine did not differ from controls. In AIDS-II patients the total FFA concentration was below normal 35% (P less than 0.01) and the stearic/oleic acid ratio was 50% above normal (P less than 0.05). The relative percentages of monounsaturated and polyunsaturated fatty acids in this group were similar to those of controls. Serum cortisol concentrations were significantly higher, 50% (P less than 0.001), but the urinary 17-hydroxycorticosteroids and 17-oxosteroids were 2-fold lower (P less than 0.001) than those of controls. Urinary creatinine did not differ from controls.
J Clin Endocrinol Metab 1992 May;74(5):1045-52. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Grunfeld C, Pang M, Doerrler W, Shigenaga JK, Jensen P, Feingold KR. Infection causes disturbances in lipid metabolism that may be mediated by cytokines. Therefore we studied plasma lipids, lipoproteins, triglyceride (TG) metabolism, and serum cytokines in three groups: patients with the acquired immunodeficiency syndrome (AIDS) without active secondary infection, patients with evidence of human immunodeficiency virus infection but without clinical AIDS (HIV+), and controls. Plasma TGs and FFA were increased in AIDS, while plasma cholesterol, high density lipoprotein (HDL) cholesterol, apolipoprotein-A-1 (Apo-A-1), low density lipoprotein (LDL) cholesterol, and Apo-B-100 levels were decreased.
J Virol 1991 May;65(5):2231-6. Human immunodeficiency virus type 1 infection of human placenta: potential route for fetal infection.Amirhessami-Aghili N, Spector SA.
AIDS Res Hum Retroviruses 1997 Sep 20;13(14):1235-42. Interaction of pregnancy steroid hormones and zidovudine in inhibition of HIV type 1 replication in monocytoid and placental Hofbauer cells: implications for the prevention of maternal-fetal transmission of HIV. Lee AW, Mitra D, Laurence J.
Folia Biol (Krakow) 1996;44(3-4):111-6. Preovulatory dynamics of ovarian steroid hormones in two mouse strains differing in the rate of meiotic maturation. Krzanowska H, Szoltys M.
J Clin Invest 1997 Apr 1;99(7):1484-91. Human chorionic gonadotropin hormone prevents wasting syndrome and death in HIV-1 transgenic mice. De SK, Wohlenberg CR, Marinos NJ, Doodnauth D, Bryant JL, Notkins AL., Metabolism 1993 Oct;42(10):1270-6.
Indices of function and weight loss in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Grunfeld C, Pang M, Doerrler W, Jensen P, Shimizu L, Feingold KR, Cavalieri RR.
Int J Health Serv 1994;24(2):311-35 Nuclear fallout, low birthweight, and immune deficiency. Gould JM, Sternglass EJ Radiation and Public Health Project, New York, NY 10024. An investigation of the mortality rates of young adults born in the postwar period of large-scale atmospheric nuclear testing (1945-1965) in the United States and other western industrial nations reveals an increasingly anomalous rise in mortality from its previous secular decline. Beginning in the late 1970s and particularly since 1983, the deterioration in the health of the 25-44 age group is related to in utero exposure to fission products in the milk and diet, associated with an unprecedented rise in underweight births and neonatal mortality known to be accompanied by loss of immune resistance. The 1945-1965 rise in the percentage of live births below 2500 grams is highly correlated with the amount of strontium-90 in human bone, both peaking in the mid-1960s. In the 1980s, for the baby boom generation (those born between 1945 and 1965), cancer incidence and mortality due to infectious diseases associated with a rising degree of immune deficiency, such as pneumonia, septicemia, and AIDS, increased sharply. This process of increasing immune deficiency appears to have been exacerbated by continuing secondary exposures to accidental reactor releases and by an acceleration of radiation-induced mutation of pathogenic microorganisms increasingly resistant to drugs.
Biokhimiia 1987 Sep;52(9):1501-11 [Activation of lipolysis and ketogenesis in tumor-bearing animals as a reflection of chronic stress states]. Chekulaev VA, Shelepov VP, Pasha-zade GR, Shapot VS.
Arkh Patol 1987;49(6):10-8 [Combination of immunodepression and disorders in nucleic acid metabolism of lymphoid tissue as a manifestation of a paraneoplastic syndrome]. [Article in Russian] Potapova GI, Shapot VS Several physiological, biochemical, and molecular biological approaches to the study of factors determining immunodepression in tumor-bearing animals are considered. Cancer cells release substances of nucleic and peptide nature that suppress the functional activity of macrophages and lymphocytes and stimulate cell proliferation in organs and tissues of the host. Suppressor T cells capable of inhibiting the function of helper T cells and impairing the differentiation of killer T cells are activated. The suppression of T- and B-cell-mediated immunity in the tumor host involves disturbances of nucleic acid metabolism in those cells as well as hypersecretion of glucocorticoids. The impairments of lymphocyte proliferation and differentiation that result in reduced immune responsiveness are attributable to drastic alterations in the metabolism of purine and pyrimidine nucleotides and to the damage sustained by the lymphocyte's DNA.
Eksp Onkol 1987;9(6):62-7 [Relation between disorders of glucose metabolism, secretion of somatotropic hormone, thyroxine, thyrotropin and hematocrit indices in rats with transplanted hepatomas]. Shelepov VP, Pasha-zade GR, Chekulaev VA, Shapot VS.
Am J Pathol 1987 Jan;126(1):103-13 Dietary fatty acid effects on T-cell-mediated immunity in miceinfected with mycoplasma pulmonis or given carcinogens by injection. Bennett M, Uauy R, Grundy SM. To test whether or not diets enriched in w-6 polyunsaturated fatty acids are significantly immunosuppressive . . . mice were fed diets enriched for fatty acids: linoleic (POLY), oleic (MONO), palmitic (SAT), or eicosapentanoic (FISH). . . . only mice on the POLY diet were significantly immunosuppressed, and only T-cell-mediated cutaneous sensitivity reactions were affected. After instillation, mice on the POLY and MONO diets were suppressed for T-cell cutaneous responses. Deliberate infection with Mycoplasma pulmonis resulted in suppressed cutaneous T-cell responses in the POLY group of C3B6F1 mice, and aspirin partially reversed the immunosuppression. Mice on the FISH diet were resistant to immunosuppression. It is tentatively concluded that diets rich in w-6 polyunsaturated diets, while not directly immunosuppressive, do predispose animals to suppression of certain T-cell-mediated immune responses. This immunosuppression can be “triggered” by infection and/or by exposure to carcinogens.
Tumour Biol 1988;9(5):225-32 Modulation of cell-mediated immune response by steroids and free fatty acids in AIDS patients: a critical survey. Nunez EA. The overall data presented in this review show that cortisol and free fatty acids, in particular long-chain polyunsaturated fatty acids, each have immunoinhibitory properties on lymphoblastic transformation of certain T lymphocytes. This effect is enhanced when the two factors are associated. These data could explain in part the immunosuppression observed in acquired immunodeficiency syndrome (AIDS) patients where enhanced concentrations of cortisol and polyunsaturated fatty acids have been observed.
Basic Life Sci 1988;49:615-20 Vitamin E and immune functions. Bendich A. Supplementation of these diets with higher than nutritionally adequate levels of vitamin E enhances immune responses. High levels of PUFA are immunosuppressive, and vitamin E can partially overcome this immunosuppression. High levels of vitamin C can protect tissue levels ofvitamin E and may indirectly contribute to the immunoenhancement by vitamin E. Severe selenium deficiency is immunosuppressive. Vitamin E can protect some aspects of immune responses from the adverse effects of selenium deficiency. These data clearly indicate that nutrients that affect the overall antioxidant status have important effects on immune functions. In addition, antioxidant nutrient interactions can synergize to overcome the adverse effects of polyunsaturated fatty acids on immune functions.
Transplantation 1989 Jul;48(1):98-102 Enhancement of immunosuppression by substitution of fish oil for olive oil as a vehicle for cyclosporine. Kelley VE, Kirkman RL, Bastos M, Barrett LV, Strom TB.
J Am Coll Nutr 1992 Oct;11(5):512-8 Role of nutrition in the management of malnutrition and immune dysfunction of trauma. Cerra FB Dept. of Clinical Nutrition, University of Minnesota, Minneapolis. Current nutrition support improves patient outcome in trauma patients. It appears to do so by limiting the adverse effects of specific nutrient or generalized nutrient deficiencies. Immunosuppression, however, continues as a significant clinical problem. This immunosuppression appears to be part of the inflammatory response that accompanies trauma, and in part, to represent the need for conditional nutrients in this setting. Three nutrients that are being evaluated include arginine, uracil as ribonucleic acid and omega-3 polyunsaturated fatty acids. Animal studies report improved immune function. Early clinical trials are reporting improved immune function and patient outcomes.
J Nutr 1996 Mar;126(3):681-92 Dietary butter protects against ultraviolet radiation-induced suppression of contact hypersensitivity in Skh:HR-1 hairless mice. Cope RB, Bosnic M, Boehm-Wilcox C, Mohr D, Reeve VE. Dietary fats modulate a wide variety of T cell functions in mice and humans. This study examined the effects of four different dietary fats, predominantly polyunsaturated sunflower oil, margarine, and predominantly saturated butter, clarified butter, on the T cell-mediated, systemic suppression of contact hypersensitivity by ultraviolet radiation. There was a linear relationship (r > 0.9) between protection against photoimmunosuppression and the proportion of clarified butter in mice fed a series of 200 g/kg mixed fat diets that provided varying proportions of clarified butter and sunflower oil. The dietary fats did not modulate the contact hypersensitivity reaction in unirradiated animals. The observed phenomena were not primary due to the carotene, tocopherol, cholecalciferol, retinol, lipid hydroperoxide or the nonfat solid content of the dietary fats used and appeared to be a result of the different fatty acid composition of the fats.
Cancer Lett 1996 Nov 29;108(2):271-9 Dependence of photocarcinogenesis and photoimmunosuppression in the hairless mouse on dietary polyunsaturated fat. Reeve VE, Bosnic M, Boehm-Wilcox C. The photocarcinogenic response was of increasing severity as the polyunsaturated content of the mixed dietary fat was increased, whether measured as tumour incidence, tumour multiplicity, progression of benign tumours to squamous cell carcinoma, or reduced survival. When mice were exposed acutely to UV radiation (UVR), a diet of 20% saturated fat provided almost complete protection from the suppression of CHS, whereas feeding 20% polyunsaturated fat resulted in 57% suppression; the CHS of unirradiated mice was unaffected by the nature of the dietary fat. These results suggest that the enhancement of photocarcinogenesis by the dietary polyunsaturated fat component is mediated by an induced predisposition to persistent immunosuppression caused by the chronic UV irradiation, and supports the evidence for an immunological role in dietary fat modulation of photocarcinogenesis in mice.
Ann Acad Med Singapore 1991 Jan;20(1):84-90. Clinical implications of food contaminated by aflatoxins.Hendrickse RG.
Arch Toxicol 1996;70(10):661-71. Host resistance to rat cytomegalovirus (RCMV) and immune function in adult PVG rats fed herring from the contaminated Baltic Sea. Ross PS, Van Loveren H, de Swart RL, van der Vliet H, de Klerk A, Timmerman HH, van Binnendijk R, Brouwer A, Vos JG, Osterhaus AD. In a semi-field study, we previously showed that harbour seals (Phoca vitulina) fed herring from the contaminated Baltic Sea had lower natural killer cell activity, T-lymphocyte functionality and delayed-type hypersensitivity responses than seals fed herring from the relatively uncontaminated Atlantic Ocean. A novel model was established to assess the specific T-cell response to rat cytomegalovirus (RCMV). When applied to the feeding study, no differences between the Atlantic and Baltic groups in the RCMV-induced proliferative T-lymphocyte responses could be detected, but virus titres in salivary glands of infected rats of the Baltic Sea group were higher. These elevated RCMV titres and changes in thymus cellularity suggest that the dietary exposure to low levels of contaminants may have been immunotoxic at a level which our immune function test could not otherwise detect. While the herring diet per se appeared to have an effect on several immune function parameters, lower plasma thyroid hormone levels in the Baltic Sea group of rats confirmed that exposure to the environmental mixture of contaminants led to adverse PHAH-related health effects.
Environ Health Perspect 1995 Apr;103(4):366-71 Dioxin activates HIV-1 gene expression by an oxidative stress pathway requiring a functional cytochrome P450 CYP1A1 enzyme. Yao Y, Hoffer A, Chang CY, Puga A. Aflatoxin B1, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) and benzo[a]pyrene cause a significant increases in CAT expression in mouse hepatoma Hepa-1 cells. We conclude that induction of a functional CYP1A1 monooxygenase by TCDD stimulates a pathway that generates thiol-sensitive reactive oxygen intermediates which, in turn, are responsible for the TCDD-dependent activation of genes linked to the LTR. These data might provide an explanation for findings that TCDD increases infectious HIV-1 titers in experimental systems and forepidemiologic reports suggesting that exposure to aromatic hydrocarbons, such as found in cigarette smoke, is associated with an acceleration in AIDS progression.
Ann Trop Med Parasitol 1997 Oct;91(7):787-93 Of sick turkeys, kwashiorkor, malaria, perinatal mortality, heroin addicts and food poisoning: research on the influence of aflatoxins on child health in the tropics. Hendrickse RG. Aflatoxin exposure occurs in > or = 30% of pregnancies in tropical Africa and the toxins are often in cord blood, sometimes at extremely high concentrations. Aflatoxins are now incriminated in neonatal jaundice and there is circumstantial evidence that they cause perinatal death and reduced birthweight. Aflatoxin-induced immunosuppresion may explain the aggressive behaviour of HIV infection in Africa. There are similarities between observations on HIV cases in Africa and those on heroin addicts in Europe, where 'street' heroin is frequently contaminated with aflatoxin. Aflatoxins were found in 20% of random urine samples from heroin addicts in the U.K. and the Netherlands.
Ann N Y Acad Sci 1986;475:320-8. Hormonal approaches to immunotherapy of autoimmune disease. Talal N, Ahmed SA, Dauphinee M.
Cell Immunol 1998 Nov 1;189(2):125-34. Estrogen increases the number of plasma cells and enhances their autoantibody production in nonautoimmune C57BL/6 mice. Verthelyi DI, Ahmed SA.
J Rheumatol 1987 Jun;14 Suppl 13:21-5. Interleukin 2, T cell receptor and sex hormone studies in autoimmune mice. Talal N, Dang H, Ahmed SA, Kraig E, Fischbach M. The administration of estrogen to pregnant mice late in gestation results in offspring with a permanently altered immune system. These mice develop features of autoimmunity similar to those that occur spontaneously in genetically susceptible autoimmune mice. This phenomenon may have etiopathological significance for familial SLE.
Endocrinology 1994 Dec;135(6):2615-22. 17 beta-estradiol, but not 5 alpha-dihydrotestosterone, augments antibodies to double-stranded deoxyribonucleic acid in nonautoimmune C57BL/6J mice. Verthelyi D, Ahmed SA.
J Autoimmun 1993 Jun;6(3):265-79 Antibodies to cardiolipin in normal C57BL/6J mice: induction by estrogen but not dihydrotestosterone. Ahmed SA, Verthelyi D.
J Autoimmun 1989 Aug;2(4):543-52. Estrogen induces the development of autoantibodies and promotes salivary gland lymphoid infiltrates in normal mice.Ahmed SA, Aufdemorte TB, Chen JR, Montoya AI, Olive D, Talal N. . . . normal mice were prenatally exposed to estrogens. . . . mice prenatally exposed to estrogens had accelerated development of autoimmune salivary gland lesions indistinguishable from Sjogren's syndrome (SS) in humans. Further experiments are warranted to confirm these findings. The prenatal effects of estrogen may have relevance for familial and neonatal autoimmune syndromes.
Isr J Med Sci 1988 Dec;24(12):725-8. Sex hormones, CD5+ (Lyl+) B-cells, and autoimmune diseases. Talal N, Ahmed SA.
Ann N Y Acad Sci 1986;475:320-8 Hormonal approaches to immunotherapy of autoimmune disease. Talal N, Ahmed SA, Dauphinee M.
Life Sci 1998;63(20):1815-22. Exacerbated immune stress response during experimental magnesium deficiency results from abnormal cell calcium homeostasis. Malpuech-Brugere C, Rock E, Astier C, Nowacki W, Mazur A, Rayssiguier Y. These studies first showed that an abnormal calcium handling induced by extracellular magnesium depression in vivo may be at the origin of exacerbated inflammatory response.
Magnes Res 1998 Sep;11(3):161-9. Early morphological and immunological alterations in the spleen during magnesium deficiency in the rat. Malpuech-Brugere C, Kuryszko J, Nowacki W, Rock E, Rayssiguier Y, Mazur A. Dietary magnesium deficiency in rodents, and especially in rats, causes inflammation and leads to alterations in the immune response.
Ann Rheum Dis 1994 Nov;53(11):749-54 Polymerase chain reaction fails to incriminate exogenous retroviruses HTLV-I and HIV-1 in rheumatological diseases although a minority of sera cross react with retroviral antigens. Nelson PN, Lever AM, Bruckner FE, Isenberg DA, Kessaris N, Hay FC.
Clin Diagn Lab Immunol 1998, Mar;5(2):181-5. Reactivity of sera from systemic lupus erythematosus and Sjogren's syndrome patients with peptides derived from human immunodeficiency virus p24 capsid antigen. Deas, JE, et al. We have previously demonstrated that about one-third of patients with either Sjogren's syndrome (SS) or systemic lupus erythematosus (SLE) react to human immunodeficiency virus (HIV) p24 core protein antigen without any evidence of exposure to, or infection with, HIV itself.
J Clin Lab Immunol 1988 Feb;25(2):101-3. Effect of diethylcarbamazine on serum antibody to feline oncornavirus-associated cell membrane antigen in feline leukemia virus cats. Kitchen LW, Cotter SM. Department of Cancer Biology, Harvard School of Public Health, Boston. Diethylcarbamazine (N,N-diethyl-4-methyl-1- piperazine carboxamide; DEC) is a drug frequently used for prevention and treatment of the filariases. An opsonic action of DEC may generate increased immune responses to microfilariae. We tested the hypothesis that DEC treatment could result in higher antibody levels to other infectious agents. A retroviral animal model was studied, in light of the consideration that use of DEC as an antifilarial agent could conceivably alter seroepidemiologic surveys as well as serologic outcomes of vaccine trials in Africa regarding human immunodeficiency virus (HIV). The effect of DEC treatment on serum antibody to feline oncornavirus-associated cell membrane antigen (FOCMA) in domestic cats exposed to feline leukemia virus (FeLV) was examined. Nine cats that tested negative before treatment tested positive (greater than or equal to 1:10 serum dilution, geometric mean titer [GMT] = 278) for antibody to FOCMA after DEC treatment. Among 19 cats initially testing positive for FOCMA antibody, higher titers were noted after treatment in 17 (pretreatment GMT = 264; posttreatment GMT = 6,158). We conclude that a history of DEC treatment should be considered in evaluating humoral responses to infectious agents. Whether use of ivermectin, a recently introduced antifilarial agent, in lieu of DEC will affect clinical expression of HIV infection in humans also warrants analysis.