SYNERGISTIC EFFECT OF CORTISOL AND HIV-1 ENVELOPE PEPTIDE ON THE NK ACTIVITIES OF NORMAL LYMPHOCYTES

In order to examine the potential role of stress hormones and circulat ing HIV-1-derived products in the progression of HIV infections, we de veloped an in vitro model system that investigates the effects of cort isol and HIV soluble gene products on the natural killer cell activity of normal lymphocytes. The system employs a 4-h Cr-51 release assay a nd K562- and LAV-infected 8E5/LAV target cells. Direct addition of cor tisol at 0.05, 0.1, and 0.2 mu g/ml or the HIV recombinant peptide, en v-gag, at 1, 10, and 50 ng/ml separately to the mixture of effector an d prelabeled target cells did not produce any significant immunoregula tory effects on NK cell activity against either target. However, corti sol or env-gag at concentrations that did not produce any inhibitory e ffect on NK activity when used separately, manifested significant inhi bitory effects when added in combination. Suppression was evident at c oncentrations as low as 1 ng/ml of env-gag and 0.05 mu g/ml of cortiso l and was observed at different effector:target cell ratios. Suppressi on was not caused by nonspecific toxicity of cortisol or HIV peptides when added in combination to the effector cells nor was due to decreas ed susceptibility of targets to lysis by effector cells. A non-HIV vir al antigen (Rubeola virus) and another HIV-1 envelope-derived sequence (env 578-608 aa) were used as controls separately or in combination w ith cortisol and did not produce significant inhibition thus demonstra ting the specificity of env-gag-induced inhibition. The synergistic in hibitory effect of cortisol-and HIV-derived soluble products in patien ts with HIV infections are consistent with a model that proposes that stress and circulating HIV-1-derived products may be involved in the p rogression of HIV infections. (C) 1995 Academic Press, Inc.