If you've read some of the other pages I wrote here, you'll remember how I talked about stress generating molecules that possess potent qualities, especially the "pro-infalmmatory" TNF-alpha and the "anti-inflammatoyr" IL-10. You will also remember that the kinds of fatty acids in your cells have a significant effect on the response. The omega 6, arachidonic acid, promotes chronic inflammation and anti-inflammation; the long-chain omega 3s promote strong inflammation, but not much in the way of anti-inflammation, though because the symptoms of anti-inflammation have been associated with inflammation, the omega 3s are said to be anti-inflammatory (they also counteract AA metabolites); the omega 9, Mead acid, generates a powerful, but quick inflammatory response, and then a powerful and quick anti-inflammation.

As I've said in another essay, the last time there was an "infectious disease" that several family members fell ill to, I barely experienced symptoms, relative to what I've experienced with AA in my cells; first, my throat felt minor pain upon swallowing, and then minor sinus congestion, an occasional sneeze and cough, and mild fatigue, and it lasted about a week. In the past, the throat was more painful, and that lasted twice as long. The cough, sneezing, and congestion were also more pronounced and lasted longer. Overall, it usually took at least two weeks to "clear." My relatives who "caught" the same thing experienced major fatigue and very severe symptoms overall, and their bouts lasted longer. One had to try two different antibiotics. I took nothing, and did nothing unsusual.

According to what is known, the sore throat should be related to TNF-alpha, whereas the coughing/sneezing and congestion would be due to IL-10. Since fatigue does not occur at first, there is no way to know whether it is due mainly to the effect of TNF-alpha or the IL-10. Moreover, it is possible that both may be responsible.

Now certain claims have been made about perceived phenomena, such as "chronic fatigue syndrome" and "AIDS" with regard to TNF-alpha, IL-10, and similar molecules. Some claim that there is too much IL-10 in "CFS" and a shift from TNF-alpha to IL-10 in "AIDS," but unless the levels of these molecules are determined at different points during the "illness," and even during the course of a day, there is no way to know at this point.

But there is a different way of thinking about this. We hear about "good" and "bad" cholesterol in the media, with prominent "experts" making such remarks, and it's the same thing with molecules like TNF-alpha and IL-10. Both are necessary, and what matters is the context - there is no villian and hero. With AA in your cells, both are "hyped up" and can cause damage, whereas with the omega 3s, molecules like TNF-alpha are enhanced but IL-10 appears to be inhibited. With Mead acid, there is a short response for both, which means that it is not likely that your body will be damaged or become dysregulated by the exposure to the "pathogen," "irritant," "allergen," or "toxin." As I've said in other essays, it is about minimizing the damage the "immune system" can do to specific cells or tissues in its effort to protect the body as a whole, and not about taking a TNF-alpha pill or an IL-10 pill, or a pill that suppresses or enhances one or the other. If one is in an "emergency" situation, then "therapeutic" doses of such substances may be necessary to stave off immediate death, but the overwhelming majority of the time, it is not about suppressing one or enhancing the other, but rather what's best is to have a short burst of the inflammatory followed by a short burst of the anti-inflammatory, and this does not happen when your body is made hyper-reactive by the unstable omega 3 and omega 6 polyunsaturated fatty acids.

Another important point is that with AA in your cells, the threshold for the inflammatory response is much lower (compared to Mead acid, at least). This means that "allergies" that a person has might never have developed in the first place if he/she had Mead acid instead of AA in his/her cells. The explanation I have furnished here accounts for the Janus-like quality of the phenomenon, that is, we hear about attempts to "boost the immune system" and also about the benefits of substances that "reduce inflammation." How is it possible to want two things that contradict each other at the same time? It just shows how little the people making such claims understand. My point, that with Mead acid in your cells you get a strong but quick inflammation and then a quick resolution to it, solves this "riddle" that is befuddling the "experts," though many act as if there is no contradiction here, which may be the most frightening aspect of this, at least on an intellectual level. With the highly unstable arachidonic acid in your cells, minor stressors generate the inflammatory process, and a cycle of damage and "rebuilding" occurs, causing so much chaos to the "system" that eventually major failure will happen, whether it be an auto-immune problem, immunosuppression, cancer, tissue degeneration, or fibrotic changes that interfere with the functioning of a particular tissue or organ.

A recent report (5/3/06) on sciencedaily.com makes some very key points on this topic, yet also demonstrates where there is a major misunderstanding, which is responsible for the poor state of affairs with respect to the practical applications of the scientific findings:

"Human T cells respond much more robustly than chimpanzee [and other primate] cells do..." and this can "...account for the rarity of T-cell mediated liver damage, such as chronic active hepatitis, cirrhosis and cancer, following Hepatitis B or C infection in chimpanzees. In addition, several other common human T cell-mediated diseases, including bronchial asthma, rheumatoid arthritis and type 1 diabetes, have, so far, not been reported in chimpanzees or other great apes."

Moreover: "This study may also explain the severe human reactions observed in a recent clinical trial using a T cell activating anti-CD28 antibody produced by TeGenero, Inc. All six healthy volunteers who received doses at 500 times lower than what was tested in nonhuman primates became severely ill, requiring hospitalization."

The volunteers experience a hyperactive immune/inflammatory response that was nearly deadly. Thus, it's clear to those who possess some familiarity with the phenomenon that the problem is the hyperactivity, and this appears to be greatly enhanced by AA as well as long-chain omega 3 PUFAs (such as EPA). However, where they do terribly wrong is in their notions about the "germs" or "bugs" causing the "disease," leading them to make prescriptive suggestions that do much more harm than good, even though attentuating the immune/inflammatory response is very easy (and inexpensive) to do.

Let's take an example - here's what they say about "HIV/AIDS:"

"The study suggests that the expression of Siglecs [which are absent in human T cells] on chimpanzee T cells in essence puts the brakes on the cells during chronic HIV infection, preventing progression to AIDS in chimpanzees. In contrast, the onset of human AIDS occurs more rapidly due to the loss of T cells..."

This makes no sense whatsoever. Apparently, they think that "HIV" activates the T cells, which then get infected with the "HIV," and are killed off. However, this has never been demonstrated, though several attempts at doing so have failed, and thus they seem to hold notions that may be common, but are incorrect. If you want to read more about this, click on "links" and then click on the Perth Group. The key point here is that when the T cells are activated, they produce cytokines that do the damage, no matter what pathogens are present or absent.

At least one of the researchers appears to be aware of what I am suggesting: "...said Varki. 'It is reasonable to hope that drugs can be found to turn the Siglec brakes back on again in human T cells, to slow the T cells down when they become hyper-active and cause disease.'"

He also understands what happened to the volunteers in the other study that resulted in the hyperactive response that was nearly deadly:

"'In retrospect, the absence of natural restrictions on activation, such as that provided by Siglecs, could have predicted this striking disparity between humans and nonhuman primates,' said Varki. The human volunteers could have experienced rapid activation of T cells and a resulting 'cytokine storm.'"

Note that TNF-alpha is a cytokine.

The only thing Varki probably does not understand is how much of a difference diet can make, because just about everyone in nations like the USA are overloaded with AA these days.

Source for the above quotations: http://www.sciencedaily.com/releases/2006/05/060502224533.htm

Relevant study: Title: "Dietary fish oil increases tumor necrosis factor secretion but decreases interleukin-10 secretion by murine peritoneal macrophages."

J Nutr. 2002 Dec;132(12):3740-3.

This study is important because of the claims about fish oil being "anti-inflammatory." Actually, the fish oil appears to attenuate the anti-inflammatory component of the process, but because "experts" noticed that symptoms commonly thought of as being signs of "inflammation" are lessened by fish oil, they call fish oil "anti-infammatory." Instead, with fish oil, there is damage from the TNF-alpha, but it just keeps going until the stressor is removed, which can result in tremendous damage. This is pointed out in the professional nutritional literature, for example, the book "Modern Nutrition in Health and Disease," by Shils and Young, or "Diet and Health," by the National Research Council.

In the 7th edition of the Shils and Young book, page 102, we learn that the "the "data certainly do not support the widely published assumption that n-3 fatty acids possess a specific retarding effect on atherogenesis... in rabbits at least, they seem to stimulate atherosclerosis." The animals had liver damage as well as "Periportal fibrosis, lipogranulomas filled with lipofuscin, and bile duct hyperplasia."

The authors go on to say: "Other potentially harmful effects of 20:5 n-3 and 22:6 n-3 [that is, EPA and DHA] rich fish oils are neglected by the advocates of increased human consumption of fish oils. The pathologically increased bleeding times, as observed after aspirin ingestion, also occurs in Eskimos on a high fish oil diet." The authors then talk about "a promoting role of [EPA/DHA] in the development of carrdiac necrosis and an increased sensitivity to catecholamine stress." And then they state that extreme tocopherol ("vitamin E") deficiency occurs with fish oil supplementation. Another telling quotation: "...the most severe degree of atherosclerosis was observed in rabbits fed fish oil, with a similar trend in the [flax] oil group., rather than after feeding palm oil with its high concentration of palmitic and stearic acid [saturated fatty acids]."

Some "diseases," such as "heart disease," which were rare in the early 1900s (in the USA and most other nations), may be related to arachidonic acid overload, and may indeed be attenuated in the short term by fish oil supplements, but the molecular-level evidence suggests that damage will be done that will simply mean dying of a different "disease" or a different variation of "heart disease," perhaps at an earlier age than if one had just eaten the typical diet. The differences will be related to the powerful inflammatory and anti-inflammatory response with AA in your cells, or with the powerful inflammatory and weak anti-inflammatory response with EPA and DHA in your cells (using my definitions, which are based upon the molecules produced rather than the perceptions of doctors and common notions about what "inflammation" is). The powerful responses with omega 3s and/or omega 6s generate a great deal of free radical activity, and this is what has lead to the "epidemic" of "heart disease," for example:

"...researchers have found that blood levels of the oxidized form of low density lipoprotein (LDL) are directly related to the severity of heart disease, according to a report in today's Circulation: Journal of the American Heart Association. In the two-part study, Japanese researchers also found that oxidized LDL was higher in the plaques of individuals with unstable angina than those with stable angina. Oxidized LDL (ox-LDL) is a form of LDL that has combined with oxygen. It is considered more dangerous than LDL because it promotes clogging of blood vessels." Article: "Form Of Cholesterol Singled Out As Cause Of Chest Pain, Heart Attack."

Source: http://www.scienceblog.com/community/older/2001/A/200110575.html

Anything that provokes and inflammatory response can cause a "disease," and with AA in your cells symptoms are greatly enhanced, for example:

Am Rev Respir Dis. 1985 Apr;131(4):624-32.

Production of arachidonic acid metabolites by macrophages exposed in vitro to asbestos, carbonyl iron particles, or calcium ionophore.

Kouzan S, Brody AR, Nettesheim P, Eling T.

"Consequent to asbestos deposition, alveolar macrophages (AM) accumulate at alveolar duct bifurcations where they phagocytize fibers. Because phagocytosis can stimulate the release of arachidonic acid (AA) metabolites, the possibility that secretion of these powerful mediators of inflammation might be induced by chrysotile asbestos was investigated in vitro. Rat AM were treated in vitro with chrysotile asbestos, and the cyclooxygenase products--prostaglandins, thromboxane B2 (TXB2), 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT)--and lipoxygenase products--leukotrienes (LT), hydroxyeicosatetraenoic acids (HETE)--secreted in the medium were isolated by high-performance liquid chromatography. Composition of the AA metabolites released was compared with that from those stimulated by the calcium ionophore A 23187 (20 microM) and by another particulate phagocytic stimulus, i.e., carbonyl iron beads. Calcium ionophore stimulation induced a marked release of various AA metabolites in the medium from both the cyclooxygenase pathway (HHT, TXB2, and PGE2, in decreasing quantities, respectively) and the lipoxygenase pathway (LTB4, 5-HETE, 12-HETE, and LTC4). The major product was LTB4. Treatment of the macrophages with asbestos fibers induced the release of a similar array of AA metabolites, although there were smaller amounts of LTC4 and 12-HETE, but increased quantities of PGF2 alpha. A time course study showed a steady increase in metabolite production for 1 h, followed by a plateau. In addition, the amount of metabolites released was dependent on asbestos concentrations. Phagocytosis of iron beads induced the secretion of the same metabolites as asbestos stimulation, but in larger quantities, probably reflecting the lack of cytotoxicity of the particle..."

Note that LTB4 seems to be doing most of the damage in this "disease," and that Mead acid cannot be made into LTB4.