Glucocorticoids and the immune system in AIDS

An interesting aspect of HIV disease is the immunoendocrine dialogue, via the hypothalamo-pituitary-adrenal axis, between glucocorticoids and cytokines and its potential role in HIV disease progression. This study reports recent data on the interaction between glucocorticoids and the immune system in AIDS patients with an acquired form of glucocorticoid resistance. Clinically, glucocorticoidresistant AIDS patients (AIDS-GR; about 12% in our series of patients) present Addisonian symptoms (weakness, weight loss, hypotension, hyponatremia and intense mucocutaneous melanosis) in spite of elevated values of plasma cortisol and urinary free cortisol. Monocytes from these patients have a significantly lower receptor affinity (higher K d) for glucocorticoids and a higher receptor density than other patients and controls. Such receptor alteration is associated with higher values of plasma interferon alpha (IFNα). In AIDS-GR there is a significant correlation between the values of receptor K d and of plasma IFNα (r=0.77). After poly(I):poly(C) stimulation, monocytes from AIDS-GR produce much more IFNα than other AIDS patients. While in patients with no resistance and in control patients, monocyte production of IFNα is inhibited by dexamethasone (the effect being reversed by RU-486), a very slight inhibition of dexamethasone on IFNα production is observed in monocytes from AIDS-GR. In conclusion, these data demonstrate that the immunosuppressive mechanisms acting in AIDS may be reversed, as shown by the increased stimulus on IFNα production found in cortisol-resistant patients. These data also suggest that antiglucocorticoid drugs may be helpful in HIV disease as they antagonize the excessive immunosuppression induced by the increased production of glucocorticoids found at every stage of HIV disease.