A possible role for the cortisol/anticortisols imbalance in the progression of human immunodeficiency virus.
The progression of HIV infection is accompanied by complex alterations in the production of adrenal steroids. Cortisol levels are increased in HIV infection whereas those of dehydroepiandrosterone (DHEA), a physiologic antagonist of the immunoregulatory activities of cortisol, decrease. The progression of HIV infection to AIDS is also characterised by a shift from a type 1 to type 2 cytokine production. Thus, defective production of interferon gamma (IFN gamma), interleukin (IL)-2, and IL-12 as well as increased production of IL-4, IL-5, IL-6, and IL-10 are observed in HIV-seropositive individuals and are proposed to be in vitro immunologic marker of progression. Cortisol and pharmacological doses of glucocorticoids (GC) suppress IL-2 and IFN gamma production and favour the production of IL-4. Furthermore, GC and IL-4 stimulate the differentiation of B lymphocytes into IgE producing plasma cells, the concentration of which augments in HIV infection. Finally, GC induce programmed cell death (PCD) in a variety of different cells, including mature T lymphocytes, and type 2 cytokines were recently proposed to augment the susceptibility of T lymphocytes to PCD. It was suggested that the progressive shift from type 1 to type 2 cytokine production characteristic of HIV infection could be at least partially provoked by the increase in the production of cortisol and the reduction of DHEA. This hypothesis is discussed within the scenario of an endrocrinologic imbalance being responsible for HIV progression at least partially via increased susceptibility of HIV + CD4 lymphocyte to PCD.
Clerici
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M
Cattedra di Immunologia, Università degli Studi di Milano, Padiglione L.I.T.A., Ospedale L. Sacco, Italy. mago@imiucca.csi.unimi.it
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Piconi
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Fusi
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Ruzzante
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Clerici
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Villa
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D018450:Disease Progression; D015658:HIV Infections / Q000097:blood* / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000276:immunology
D006854:Hydrocortisone