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

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 cytekines, 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-γ were measured by enzyme-linked immunosorbent assay. AIDS-C patients showed low IL-2 and high IL-4, IL-10, and IgE concentrations: 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.