Library:Autoimmunity

A Ray Peat newsletter.

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Ray Peat's Newsletter "Reason can answer questions, but imagination has to ask them." Ralph W. Gerard Copyright 2005 Raymond Peat P.O. Box 5764 Eugene OR 97405 May 2006 Not for republication without written permission.

Autoimmunity The thymus gland is important for growth and fertility, but it is now considered to be an important regulator of the immune system. As the gland shrinks with aging, the incidence of "autoimmune diseases" increases, possibly because the regulatory functions ofthe gland have been lost.

It has been shown that radiation, polyunsatu-rated fatty acids, estrogens, and heavy metals and other toxins including dioxins damage the thymus gland, and can produce immunodeficiency. These stressors also stimulate the "autoimmune" antibodies.

Estrogen shrinks the thymus and blocks NK cells, and blocks cell division in thymic cells. Thyroid stimulates regeneration of the thymus, even after age-related atrophy. Progesterone protects against the thymic atrophy produced by stress and cortisol, and promotes thyroid's effects, and protects against many of the conditions that are called "autoimmune." Estrogen creates both immunodefi-ciency and autoimmune degenerative conditions.

Hypothyroidism causes the thymus gland to atrophy , partly because the thyroid hormone itselfis essentialfor the maintenance ofthe gland, and also because hypothy-roidism is likely to be accompanied by excessive levels ofestrogen and cortisoL Polyunsaturated fatty acids interfere with the formation ofthe thyroid hormones, by preventing the coupling reaction, which converts iodotyrosine residues into iodothyronine residues in the thyro-globulin. The resulting abnormal thyroglobulin is antigenic.

Animals that are fed diets that completely lack the polyunsaturated fatty acids appear to be free of the autoimmune diseases: their tissues can even be transplanted into other animals with less antigenicity than is normal, so the dietary polyunsaturatedfatty acids seem to be involved in the development of the abnormally increased antigenicity of the various autoimmune degenerative diseases.

Several years ago, I wrote about Metchnikov's theory of immunity, based on the role of the phagocyte in the organism's ordinary growth, and I also argued that inflammation was a pathological reaction, rather than being a healthy part of a defensive immune system. Since then, the role of inflammation has been recognized in heart and circulatory disease, Alzheimer's disease, and other diseases, and even in obesity, diabetes, depression, and osteoporosis, so that now it isn't a universal medical reflex to think of inflammation as a purely normal physiological response. However, the history of treating inflammation as part of the immune system" has left a residue of medical ideology, in which a pathogenic organism must be invoked as the cause of any inflammation, even though the concept of "sterile inflammation" has a strong foundation of evidence.

Metchnikov's view, that the "immune system" is a constructive part of normal physiology, combined with the idea of inflammation as a pathological hindrance to normal functioning and development, forms the framework for a major reconsideration of the functions of antibodies, the thymus gland, lymphocytes, and other parts of "the immune system." A few people (Jamie Cunliffe and Polly Matzinger, for example) are working on this new paradigm of "immunity," challenging the "assumption that the immune system ... has evolved to find, kill and eliminate foreign organisms." If they are right, then all of medical thinking about immunity since Metch-nikov's ideas were discarded has been, effectively, an attack against a full and proper understanding of the nature of the organism, and specifically has led to a deep misunderstanding of growth, regeneration, aging, cancer, and the functions of nerves, honnones, and tissue interactions.

A pathogen is usually defined as an organism or a substance that causes tissue damage. I think the definition should be "a substance or process that causes tissue damage," to include the patho-genic effects ofmalnutrition, stress, and radiation, for example. The consequences of tissue damage have to be distinguished from the causes of tissue damage. The failure to distinguish cause and effect has led to many foolish medical theories.

The new orientation toward the immune system is that its main function is to clean up the debris created by developmental processes (such as the elimination ofred blood cells, or the regres-sion of the tadpole's tail), or by injury, and to prepare the system for recovery or regeneration. This orientation brings together ideas from devel-opmental biology and immunology in a very encouraging way. For example, a recent study shows that "autoimmune" antibodies are involved in brain repair after traumatic injury.

The example of the tadpole's tail provides a metaphor that might be useful in understanding the ways in which honnones and the immune system interact in mammals and people. Without the thyroid honnone, a tadpole keeps its tail, and fails to turn into a frog, though it keeps growing. The thyroid honnone causes the animal to progress to a higher stage of development, in which it has a higher metabolic rate and uses lungs rather than gills. The phagocytic cells rapidly consume the structures that were appropri-ate for the lower stage of development and metabolism.

I think we can see analogous processes in the functioning of our immune system. When cells in any part of the body aren't able to maintain an efficient energy metabolism, they tend to be replaced by new, more active cells, and the debris of the old cells is removed by phagocytosis, often without detectable inflammation. Stimulation and adaptation are always causing remodeling of our bodies, with bones growing along lines of stress, areas of the brain expanding with learning, and organs such as the intestine and liver modifYing their metabolism according to diet and exposure to toxins.

Inflammation, atrophy, or tumefaction can occur when some part of the regenerative and developmental process is defective. A failure of energy metabolism can be seen in each of these types of problem. Usually, prolonged inflamma-tion leads to atrophy and fibrosis, which in turn increases the likelihood that a tumor will develop.

Two organs that can change their mass greatly in a short period of time are the thyroid and the thymus.

The thyroid can be functionally suppressed, and, with stimulation, return to full activity within a few hours. If it is stimulated continuously, it can increase its mass greatly in a few days. The thymus can lose most ofits mass in a few hours.

The remarkable ability of the thymus gland to shrink rapidly when it's exposed to estrogen or stress or cortisol is very probably related to the fact that "cleaning up messes" is a primary function ofmany ofthe cells that constitute it.

Most of the cells of the thymus are very dependent on sugar metabolism, and this is disturbed by stress, cortisol, estrogen, and some kinds of fat. Even under nonnal conditions, there is a rapid turnover of its cells. Many of the cells that make up the thymus, like leukocytes gener-ally, are highly sensitive to anything that limits their energy.

These changes in the size and composition"of the thyroid and thymus glands involve some ofthe biochemical processes that are involved in the developmental changes in tadpoles and frogs.

Inflammation occurs when the production of debris is too rapid for its quiet removal, as when energetic process fail, or when certain specialized organisms interact destructively with the tissues. The characteristic changes in metabolism, a shift toward the production oflactic acid and the break-down of protein, are probably as much the cause of inflammation, as its effect.

Estrogen is an important regulator of energy metabolism, and it is therefore crucially involved in the diseases known as "autoimmune diseases."

Progesterone, thyroid, and various nutrients including vitamin E, oppose the actions of estrogen, and so have a role in the prevention of the "autoimmune diseases."

These diseases include rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, Devic's optic neuritis, cystitis, and various types of hepati-tis and nephritis and pancreatitis.

Aging and stress are estrogenic, and this estro-gen effect leads to atrophy of the thymus, combined with inflammation. The associated cortisol excess decreases the inflammation, but aggravates the disregulation of the immune system. Serotonin is another stress-related factor that produces involution of the thymus .

The thymus gland permits immune cells to mature and to become organized. It is a major factor in the regulation of the cells that produce antibodies, the B (bone marrow derived) lympho-cytes, and when the thymus is chronically damaged, the production of antibodies tends to increase, but without the sensitive control the thymus provides. Thymus-type cells are produced not just in the thymus, but also in other organs, especially the liver.

In the young organism, the disruption of a tissue exposes a variety of antigens from the differentiated cells. Antibodies that are formed to these antigens have two very different functions. They stimulate the removal of the defective cells and debris, and they locally obscure the specifi-cally differentiated tissue components, creating a sort ofvacuum to be filled by the multiplication of undifferentiated "stem" cells, which repair the damaged region.

One line of research in developmental biology emphasizes the innate tendency of cells to grow and multiply, with differentiation and growth inhibition being the subsequent result of interac-tions with their environment.

For many years, researchers such as Szent-Gyorgyi searched for general or specific inhibitors of cellular multiplication. Szent-Gyorgyi gave the name "rerin" to a molecule that he thought could restrain cancer growth. Leonell Strong studied liver extracts, and found several anticancer agents. W.S. Bullough extracted materials that were tissue specific, that he thought might synergize with adrenaline in restraining tissue growth.

About 50 years ago, an experiment with developing frogs' eggs encouraged this line of research. The experimenter found that when the juice extracted from a particular tissue was added to the water in an aquarium where frog eggs were starting to develop, the developing embryo had a deficiency of that particular tissue, and its devel-opment would stop when the absence or deficiency ofthat tissue became limiting. In rats, a similar organ-specific substance had been suggested by removing part of the liver of one rat of a pair that shared the same blood supply. The livers of both animals grew until the total mass was appropriate for two animals, but the operated liver stopped growing prematurely, apparently because a circulating growth inhibiting substance reached a certain level. Bullough's term "chalone" has been generally accepted as the name for such growth inhibiting substances.

I suspect that the immune system, and the "autoantibodies," can have a function comple-mentary to that ofthe chalones, possibly by block-ing the release ofchalones.

In 1970, I. Hellstrom and K.E. Hellstrom showed that cancer growth is promoted by an antibody, and later they showed that antagonists to that antibody would allow the cancer to be suppressed. Their work is still progressing, and it is probably relevant to both the chalone theory, and to the processes of autoimmunity and tissue regeneration. Proper control in the immune system is very closely associated with the processes that maintain a proper balance between tissue growth and tissue atrophy. Too much of an anti-chalone agent would produce a tumor, but too little would lead to atrophy when stress-damaged tissues weren't replaced.

Recent work by M. Bissell and V. Weaver shows results parallel to the Hellstroms', but involving the interactions of cells, extracellular matrix, and antibodies.

The healthy thymus gland, which depends on a properly functioning thyroid gland, is essential for close regulation of the antibody-producing cells. With aging and the various stressors, the immune system tends to over-produce antibodies, as the cell-mediated process become weaker. This is similar to the changes produced by estrogen . It's generally accepted that the thymus is responsible for preventing the production of autoimmune antibodies. I suspect that its actions are more subtle, and that it is (or can be) involved in devel-opmental and regenerative processes.

Animal studies of autoimmune degenerative diseases show that estrogen promotes autoimmu-nity, and that progesterone alleviates or prevents some of the typical autoimmune diseases. Their antagonistic effects on the mediators ofinflamma-tion are probably responsible, as well as their opposite effects on the activation of retroviruses and stress (or "heat shock") proteins.

Systemic lupus erythematosis, rheumatoid arthritis, and other autoimmune diseases are usually corrected by the combined use of proges-terone and thyroid, both of which help to restore the thymus gland.

Although medical people have been taught to believe that aging isn't an estrogenic state, contrary to the clear evidence that estrogen production (by the aromatase enzyme) in many tissues increases with age, an experiment has demonstrated that giving an aromatase inhibitor to old rats causes their thymus to regenerate. Now that commercial aromatase-inhibiting drugs are coming onto the market, this experiment should be of considerable interest to people involved in <fancer treatment, but its impli-cations are so important that most researchers and therapists will prefer to forget it.

The estrogenic state of old age or of stress (with increased exposure to cortisol) is partly the result of the progressive decrease in thyroid and progesterone, which is closely associated with the decline in respiratory function and mitochondrial efficiency.

The declining energy functions increase the demand for an efficient immune system, especially when we see the immune system as a regulator oftissue repair and restoration.

The accumulation of polyunsaturated fats contributes to all phases of this process of holistic decline, from the decrease of the crucial respira-tory enzyme cytochrome c oxidase, through decreased thyroid hormone activity and progester-one activity, to the activation of aromatase and estrogen and the production of tissue antigens by toxic products oflipid peroxidation.

A study in Hawaii found that men who ate tofu were more likely to have dementia and brain atrophy than men who ate a standard "western" diet. Soybeans contain estrogenic chemicals, such as genistein. In Alzheimer's disease brain metabo-lism is low. Genistein, like other estrogens, causes the thymus gland to atrophy . Since Alzheimer's disease is now often consid-ered to be an "autoimmune" disease , both preventive and curative approaches should proba-bly concentrate on protecting and restoring the energy metabolism and the thymus gland.

Besides the systemic toxic effects of dietary polyunsaturated fats, those fats appear to be a major factor in making tissues susceptible to damage from immunological reactions, since the tissues of rats that are deficient in the "essential fatty acids" are not damaged by antibodies that would seriously injure or kill "normal" tissues. . These animals are also resistant to many toxins, including endotoxin.

The unsaturation of tissue lipids increases in aging animals, along with the increased produc-tion of estrogen and decreased production of pregnenolone, progesterone, and the T3 compo-nent of the thyroid hormone. Autoimmunity increases with aging, as the thymus gland atrophies. A program to prevent or correct autoimmunity should also help to reverse the very generalized inflammatory and atrophic processes of aging. Restoration of tissue lipids (especially cardiolipin, which activates the crucial respiratory enzyme) to the high-energy state of childhood would be a central part of such a program.

Antibodies to cardiolipin are promoted by excess estrogen , and this is probably related to estrogen's antirespira-tory actions.

Rather than viewing autoimmune diseases as irreversible degenerative conditions, I think they should be viewed as problems of metabolic energy, processes of self-repair that just need a little support from improved diet and other environmental conditions. .