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re: High Cortisol
May 24, 2004

from Pubmed: "Inflammatory responses in many cell types are coordinately regulated by the opposing actions of NF-kappa-B (164011) and the glucocorticoid (cortisol) receptor. The increase in GR-beta protein expression correlated with the development of glucocorticoid resistance. NFKB has been detected in numerous cell types that express cytokines, chemokines, growth factors, cell adhesion molecules, and some acute phase proteins in health and in various disease states. NFKB is activated by a wide variety of stimuli such as cytokines, oxidant-free radicals, inhaled particles, ultraviolet irradiation, and bacterial or viral products. Inappropriate activation of NF-kappa-B has been linked to inflammatory events associated with autoimmune arthritis, asthma, septic shock, lung fibrosis, glomerulonephritis, atherosclerosis, and AIDS. In contrast, complete and persistent inhibition of NF-kappa-B has been linked directly to apoptosis, inappropriate immune cell development, and delayed cell growth. For reviews, see Chen et al. (1999) and Baldwin (1996)" Inhibiting NFkB (selenium, turmeric, etc...) might then help resolve the thrush, geographic tongue and cheilitis. If the presence of virus in the blood stream stimulates the ccr5 receptor even transiently without infecting the cell then Haart would definitely help since it reduces cytokine receptor stimulation which also induces NFkB as well as many other cell signalling pathways which maybe one way the virus effects people differently. also from pubmed: " Using a panel of monoclonal antibodies specific for human CCR5, Rottman et al. (1997) showed by immunohistochemistry and flow cytometry that CCR5 is expressed by bone marrow-derived cells known to be targets for HIV-1 infection, including a subpopulation of lymphocytes and monocytes/macrophages in blood, primary and secondary lymphoid organs, and noninflamed tissues. In the central nervous system, CCR5 was expressed on neurons, astrocytes, and microglia. In other tissues, CCR5 was expressed on epithelium, endothelium, vascular smooth muscle, and fibroblasts. Chronically inflamed tissues contained an increased number of CCR5-positive mononuclear cells, and the number of immunoreactive cells was directly associated with a histopathologic correlate of inflammatory severity. The results suggested that CCR5-positive cells are recruited to inflammatory sites and, as such, may facilitate transmission of macrophage-tropic strains of HIV-1."

What do you think?

Response from Dr. Pierone

I think that the human body is a very complex organism and eventually we will have so much information about physiology and pathologic processes that no human being will be able to process it. As a result we will present ourselves to interactive neural networks for diagnosis and management of our various ailments. But this won't likely be available until 2525 (if man is still alive) so in the meanwhile we will have to muddle through.

One of the effects of cortisol is to reduce inflammation and suppress immune responses. This may turn out to be a positive in HIV by reducing activation of latently infected CD4 cells. Some intriguing data has come out of pilot studies of immunosuppressive agents in STI studies in HIV. We often talk about "boosting the immune system" as immunologic therapy for HIV infection. Perhaps we should be looking into cooling down the immune system in HIV infection (hmm does this patient need Ritalin or Valium?)

There is no question that HAART helps HIV-infected people with thrush, angular chelitis, and geographic tongue. The mechanism is generally related to immune improvement and secondary control of yeast (linked to all three conditions). I don't have any experience with selenium and tumeric for thrush and geographic tongue (but would not rule it out).

Finally, I am adamantly opposed to CCR-5 and think that it is harmful to those with HIV infection. The less of it floating around, all the much the better as far as I am concerned. Extensive studies of CCR-5 inhibitors are about to begin, so we should know more in the coming years.

Thanks for posting.



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