Virus effects on HPA axis/cortisol production + immune function

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HIV and the cortisol connection: a feasible concept of the process of AIDS.

Corley PA.

Recent evidence suggests that HIV infection and the clinical and laboratory manifestations of acquired immunodeficiency syndrome (AIDS) are a result of the genetic influence of the virus on cellular adrenocorticotrophic hormone (ACTH) and cortisol metabolism. Recent genetic studies substantiate this view with the observation that the HIV-1 genome is linked to glucocorticoid inducibility and to glucocorticoid receptor binding, and may explain the strong ability of cortisol to enhance HIV replication. Adrenocortical hyperactivity observed in HIV-infected individuals has been found to be independent of the hypothalamic-pituitary axis, and is apparently a result of increased ACTH production by HIV. It is proposed that the HIV-induced cortisol excess is the foundation of the immunosuppression seen in AIDS, and is the basis for alternative avenues of treatment, including the use of ascorbic acid. PMID: 7476594

Glucocorticoids and the immune function in the human immunodeficiency virus infection: a study in hypercortisolemic and cortisol-resistant patients.

Norbiato G… Department of Endocrinology, L. Sacco University Hospital, Milan, Italy.

Immunological studies in human immunodeficiency virus (HIV)-positive patients suggest that the disease progression is accompanied by a defective production of type 1 cytokines (interleukin-2 (IL-2) and IL-12], an increased production of type 2 cytokines (IL-4, IL-6, and IL-10), and an increased production of IgE. HIV infection is also associated with activation of the hypothalamo-pituitary-adrenal axis function and increased plasma and urinary cortisol concentrations. As cortisol is involved in the physiological regulation of cytokines, a study was conducted to examine cytokine patterns in two groups of hypercortisolemic patients, one with normal sensitivity to glucocorticoids and the other with glucocorticoid resistance. Ten HIV-infected patients with normal receptor affinity to glucocorticoids (AIDS-C), 10 HIV-infected patients with low receptor affinity to glucocorticoids (AIDS-GR), and 20 healthy subjects were studied. Receptor characteristics of peripheral blood mononuclear cells were evaluated by [3H]dexamethasone binding. Serum cortisol and urinary free cortisol were measured by RIA. Serum ACTH and IgE were measured by immunoradiometric assay, and IL-2, IL-4, and IL-10 cytokines and interferon-gamma were measured by enzyme-linked immunosorbent assay. AIDS-C patients showed low IL-2 and high IL-4, IL-10, and IgE concentratios; conversely, AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations. Thus, in HIV infection, elevated cortisol levels suppress cell-mediated immunity and stimulate humoral immunity, whereas this response is not detected in cortisol-resistant patients. These findings indicate that cortisol and its receptors are critically involved in the regulation of immune function in HIV infection. PMID: 9329349