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 an d cytokines and its potential role in HIV disease progression. This st udy reports recent data on the interaction between glucocorticoids and the immune system in AIDS patients with an acquired form of glucocort icoid resistance. Clinically, glucocarticoid-resistant AIDS patients ( AIDS-GR; about 12% in our series of patients) present Addisonian sympt oms (weakness, weight loss, hypotension, hyponatremia and intense muco cutaneous melanosis) in spite of elevated values of plasma cortisol an d urinary free cortisol. Monocytes from these patients have a signific antly lower receptor affinity (higher K-d) for glucocorticoids and a h igher receptor density than other patients and controls. Such receptor alteration is associated with higher values of plasma interferon alph a (IFN alpha). In AIDS-GR there is a significant correlation between t he values of receptor K-d and of plasma IFN alpha (r=0.77). After poly (I):poly(C) stimulation, monocytes from AIDS-GR produce much more IFN alpha than other AIDS patients. While in patients with no resistance a nd in control patients, monocyte production of IFN alpha is inhibited by dexamethasone (the effect being reversed by RU-486), a very slight inhibition of dexamethasone on IFN alpha production is observed in mon ocytes from AIDS-GR. In conclusion, these data demonstrate that the im munosuppressive mechanisms acting in AIDS may be reversed, as shown by the increased stimulus on IFN alpha production found in cortisol-resi stant patients. These data also suggest that antiglucocorticoid drugs may be helpful in HIV disease as they antagonize the excessive immunos uppression induced by the increased production of glucocorticoids foun d at every stage of HIV disease. (C) 1997 Elsevier Science Ltd.