Immune, Oxidative and Metabolic Imbalance
AIDS is characterised by a persistent oxidative imbalance. An increasing deficiency of glutathione plays a crucial role in the transition from pre-AIDS to full blown disease (1,2). Glutathione, the major, water soluble antioxidant in the body, protects cells from oxidative damage. It does not enter most cells directly and therefore must be made inside the cell, from its three constituent amino acids: glycine, glutamatic acid and cysteine. One important role of glutathione is to suppress damaging overproduction of nitric oxide (NO) gas by cells.
Certain types of immune system cells eliminate microbes by producing nitric oxide (NO) gas. There must be a balance between NO gas-producing immune cells and those that do not produce NO gas. This balance between cellular and so-called humoral (antibody) immunity can be disturbed by non-infectious as well as infectious factors, and can lead to an acquired deficiency in cellular immunity (AIDS). Over-stimulation of an immune cell's NO gas production that is either too strong or lasts too long leads to compensatory inhibition of NO gas production as a protective response and increased activation of antibody-producing cells. The end result can be an uninhibited rise in opportunistic microbes such as fungi, parasites, mycobacteria, and viruses within the body's cells that would normally be eliminated without symptoms by NO gas.
During the NO gas defence process, cells, including NO gas producing cells, must be protected from potential damage and accelerated death caused by NO gas production and this is an important role of antioxidants. Nutritional intake must be sufficient to provide for the availability of antioxidants inside cells during this NO gas defence process and other NO inducing processes. If antioxidant supplies are insufficient or used up by various combinations of oxidising agents, toxic and pharmatoxic substances, malnutrition or lack of nutrition, foreign protein intake, chronic infections, lack of hormone regulation, emotional stress, etc. the NO gas production can no longer be neutralised sufficiently. This causes increased cell breakdown and cell-biology counter reactions to occur in immune cells and non-immune cells, the ultimate result of which is the effective switch off of immune cell NO gas production.
T-cells are particular types of cells important in cellular immunity. According to the Establishment, AIDS is the result of HIV decreasing a subset of T-cells known as CD4 cells, although it cannot explain how this happens. There are two types of CD4 cells: Th1 cells and Th2 cells (3). Th1 cells stimulate cellular immunity and produce NO gas, they are prone to damage from their own NO gas production when their glutathione level is insufficient. They produce inflammatory immunological messenger chemicals called cytokines that stimulate macrophages. Macrophages ingest invading microbes (a process called phagocytosis) and kill them using NO gas. Another important role of macrophages is the removal of dead and damaged cells and cell debris, again by phagocytosis. When Th1 function is impaired or suppressed these macrophage functions are suppressed. Th2 cells stimulate antibody production, they donít produce NO gas and so are not prone to damage by their own NO gas production.
Under conditions of persistent oxidative and nutritional stress the persistent over-production of NO gas (necessary for cellular immune defence) cannot be countered by an adequate supply of antioxidants, particularly glutathione. The body responds to this condition by releasing cortisol (an anti-inflammatory hormone) and reducing the number of T-cells that mature into Th1 cells, they mature into Th2 cells instead. When the glutathione level is low in types of cells called antigen presenting cells (this is another role of macrophages) they direct immature CD4 cells to mature into Th2 cells rather than Th1 cells (4). This role of macrophages is therefore stimulated. The Th2 cells migrate to the bone marrow where they stimulate antibody production, hence the low T-cell count attributed to HIV. Note that the T-cell count performed by the AIDS establishment does not distinguish between Th1 and Th2, it counts all CD4 that are in the bloodstream and does not take account of any CD4 cells in locations outside the bloodstream, such as the bone marrow, where the vast majority of such cells are. Once antibody production, resulting from increased Th2, exceeds an arbitrary threshold level, a positive HIV test occurs. Even the use of recombinant (genetically engineered) proteins (never proven to belong to HIV anyway) in the HIV test cannot prevent the binding of non-specific antibodies, this is why the HIV tests called ELISA tests use blood serum dilution factors. If the oxidative stress continues unabated then the system responds by effectively switching off immune cell NO gas production. The observation that antibody level continually rises (because more and more CD4s mature into Th2 rather than Th1) in HIV positives means it is impossible for HIV to cause AIDS (by destroying or reducing CD4 cells) this is because the role of type 2 CD4 cells (TH2 cells) is to stimulate antibody production.
The human organism responds to various psychological, toxic, infectious, traumatic or nutritional stresses with an activation of the hypothalamus, the pituitary gland and the adrenal gland. The hypothalamus-pituitary-adrenals is called the neuroendocrine stress axis. This has survival value in "fight or flight" situations because it initiates reactions of the catabolic (cellular substance breakdown) metabolism in order to liberate energy quickly. The adrenal gland releases hormones called glucocorticoids and cortisol to contain inflammatory damage caused by this process, these hormones are natural glucocorticosterioids which suppress inflammatory cellular immune responses (12). A persistently raised cortisol level in the blood (known as hypercortisolism) impairs the cellular immune responses associated with Th1 cells. A high cortisol level causes Th2 cells to migrate to the bone marrow (5) where they activate antibody producing cells (B-cells). The activation of B-cells, and their subsequent antibody production, is also enhanced by cortisol (6). People who are at risk of getting AIDS have a persistent catabolic (cell breakdown) metabolism. For information on the important causal connection between AIDS and medical treatment with glucocorticosterioids you are referred to
AIDS is primarily a result of persistent oxidative stress which manifests as a persistently low antioxidant level in general and of a particular protective chemical group, called a sulphydryl group, in particular. The sulphydryl (SH) groups are lost as a result of a chemical process called oxidation. The body provides sulphydryl groups in the form of glutathione. The sulphydryl groups (either from glutathione or its precursor cysteine) protect body structures by reacting with oxidising agents that would otherwise damage cells, the SH content of cysteine containing proteins is crucial for the transfer of oxygen through cell membranes. One effect of the loss of sulphydryl groups in cells is the polymerisation of a protein called actin which makes up the skeleton of cells. This leads to a weakening of the cell membrane which eventually kills the cell. It also activates nucleases (enzymes which breakdown DNA and RNA) and proteases (enzymes which breakdown proteins) within cells so that, with increased cell death, fragments of DNA, RNA and proteins reach the extracellular space in large amounts. Auto-antibodies generated against these cellular fragments can cause a false positive HIV test.
AIDS and the Drug Connection
Mitochondria are the energy factories of cells. Their DNA is not protected by the cell nucleus. There is no nuclear repair mechanism for mitochondrial DNA because mitochondria are outside the nucleus, they are dispersed within the fluid (known as the cytoplasm) surrounding the nucleus. Exposure to oxidising agents provides a source of harmful chemicals called free-radicals that can damage cells and mitochondrial DNA. The damage to mitochondrial DNA can be cumulative.
Treatment with nucleoside analogues (AZT, ddI, 3TC etc.) and with Septrin (Bactrim) and related antibiotics has a very adverse effect on mitochondria. As oxidising agents these drugs reduce oxygen transport into cells by oxidising thiol groups. This oxygen is needed for the production of ATP (the chemical fuel of the cell) in mitochondria in a process called oxidative phosphorylation. In addition they inhibit the synthesis of mitochondrial DNA, which also decreases the production of ATP. The reduction of ATP leads to an increase in free-radicals, which are themselves highly reactive oxidisers. Once the level of ATP declines to a certain level and the molecules which normally remove harmful free-radicals are all used up, these excess free-radicals cause even more mitochondrial DNA damage and therefore an even greater reduction in ATP, more free-radicals and therefore even more mitochondrial DNA damage, a vicious circle. The cell initiates programmed cell death. This effect is particularly severe in rapidly maturing cells with high turnover, such as CD4 cells. Note that the anti-HIV drugs and Septrin destroy or suppress the bone marrow where all immune system cells are born!
A major group of oxidising agents are recreational drugs. Nitrite inhalents (poppers) are particularly severe oxidising agents promoting cell damage and antioxidant deficiency. The unprecedentedly high usage of nitrite inhalants (poppers) which were an integral part of the gay scene from about 1974 was an important contributor to early Western AIDS. Their use spread into the heterosexual community 4 or 5 years later. To quote Newell et al (7) "These products have been found to be profoundly immunosuppressive for human lymphocytes [immune system cells] in vitro" See also Hersh et al. (8) and Goedert et al. (9). In addition, the widespread homosexual use of particular benzene derived lubricants from 1978 onwards may have been a factor providing accelerated progression to AIDS in early cases due to bone marrow suppressive effects.
A major contributing factor to early Western AIDS was the use of Septrin (also known as Septra, Bactrim, Co-trimoxazole) with impunity from the early 1970s onwards to treat a wide range of microbial infections, mostly in sexually active homosexuals, especially stubborn urinary tract infections, intestinal infections and atypical pneumonias.
Septrin is a combination of two substances, sulphamethoxazole and trimethoprim. Trimethoprim is used to treat leukaemia. It does this by killing white blood cells, which happen to be collectively the cells of the immune system! Sulphamethoxazole inhibits the synthesis of folic acid and trimethoprim inhibits the conversion of folic acid into tetrahydrofolate. Without tetrahydrofolate, essential precursors for new DNA cannot be synthesised. Inhibition of this essential metabolic pathway for growth, cell differentiation and division causes the faulty development of nucleic acids, enzymes and other proteins or ends this development completely. The damaging consequences for mitochondrial DNA are considerable because it does not benefit from nuclear DNA repair mechanisms. Septrin is used to treat PCP but the fungus causing PCP eventually develops resistance to Septrin, the field is then wide open for this fungus because of the damage done to cellular immunity
AIDS in Africa
In Africa a vicious circle can sometimes arise whereby persistent malnutrition and/or high exposure to chronic infections and inflammations causes antioxidant deficiency and suppression of cellular immunity leading to further chronic infection, compounded antioxidant deficiency and so on. This is AIDS in Africa.
AIDS-causing conditions in the west (Septrin, anti-HIV drugs, Poppers etc.) are generally more hostile to T-cells than AIDS causing conditions in Africa. For this reason PCP is quite rare in Africa (see notes 10 and 11) except in young children. This is partly because immature CD4 and CD8 cells (which mature in the thymus) are prone to destruction by cortisol but mature T-cells are resistant (13). The immature and inexperienced immune systems of young children are more vulnerable to such effects.
The vast majority of Western AIDS patients sooner or later get PCP, it is the typical AIDS defining disease in the West. The PC fungus is just as ubiquitous in Africa as it is in the West so if HIV were really the cause of AIDS, PCP would be as prevalent in African "AIDS patients" as it is the West. The prevalence of PCP in Africa will only start to resemble that in the West when Africans have been liberally showered with the "anti-HIV" poisons.
The loss of cellular immunity that characterises AIDS and renders the body open to opportunistic infections occurs as follows:
AIDS is a manifestation of a cumulative imbalance in fundamental and interrelated oxidative, metabolic and immunological processes caused by a variety of either direct or indirect oxidative and/or nutritional stressors.
References and Notes
1. FASEB J., 1997, Vol. 11:1077-1089
2. Proc. Natl. Acad. Sci. USA, 1997, Vol. 94:1967-1972
3. Ann. Rev. Immunol., 1989, Vol. 7:145-173
4. Proc Natl Acad Sci USA, 1998, Vol. 95(6):3071-6 5. Immunology, 1975, Vol. 28:669-680
6. Journal of Immunology, 1977, Vol 119(2):598-603
7. Pharmacotherapy, 1984, Vol. 4:284-291
8. Cancer Research, 1983, Vol. 43:1365-1371
9. Lancet, Feb 20, 1982, pp 412-416
10. Quote from American Journal of Respiratory and Critical Care Medicine, 1994, Vol. 149(6):1591-1596 "Detailed investigations confirm the rarity of PCP in Africa and highlight non-specific interstitial pneumonitis as the predominant diagnosis"
11. Quote from Case Report, The Central African Journal of Medicine, 1999, Vol. 45(5):127-8 "Pneumocystis carinii [PCP] is recognised as one of the leading causes of death in AIDS patients in developed countries but its role in this regard in developing countries appears to be less prominent. Sub-Saharan African countries, in spite of their high HIV prevalence, have hardly recorded any cases"
12. Ann. Internal Med. 1976, Vol. 84:304-315
13. Medical Hypothesis 1996, Vol. 46:551-555