ALTERED ADRENOCORTICOTROPIN AND CORTISOL RESPONSE TO CORTICOTROPIN-RELEASING HORMONE IN HIV-1 INFECTION

Alterations of the hypothalamic-pituitary-adrenal (KPA) axis are commo n in HIV infection. To characterize further the site of these derangem ents and their possible causes, eight male drug addicts with symptomat ic HIV infection (stage IV C2) underwent the following investigations: repeated baseline determinations of cortisol, adrenocorticotropin (AC TH), interleukin 1 beta (IL-1 beta), IL-6 and interferon alpha (IFN-al pha); and ovine corticotropin-releasing hormone (CRH) test (100 mu g I V) for ACTH and cortisol determinations. Baseline cortisol levels were either normal dr elevated in all patients. A significant positive lin ear correlation was found between baseline levels of cortisol and both IL-6 (r=0.955; p<0.001) and IL-1 beta (r=0.863; p<0.005), but not bet ween cortisol and ACTH or between ACTH and circulating cytokines. Both ACTH and cortisol responses to CRH were nearly absent in six out of e ight patients, and delayed in the others. The areas under the curves o f both ACTH and cortisol after CRH were significantly lower in HIV pat ients than in a group of eight healthy control subjects (p=0.0157 for ACTH and p=0.046 for cortisol). Our data suggest the possibility of an inappropriate stimulation of the HPA axis in symptomatic HIV infectio n by HIV-induced release of cytokines, with a blunted pituitary and ad renal response to CRH.