Synergistic Effect of Cortisol and HIV-1 Envelope Peptide on the NK Activities of Normal Lymphocytes

Abstract

In order to examine the potential role of stress hormones and circulating HIV-1-derived products in the progression of HIV infections, we developed an in vitro model system that investigates the effects of cortisol and HIV soluble gene products on the natural killer cell activity of normal lymphocytes. The system employs a 4-h 51Cr release assay and K562- and LAV-infected 8E5/LAV target cells. Direct addition of cortisol at 0.05, 0.1, and 0.2 μg/ml or the HIV recombinant peptide, env-gag, at 1, 10, and 50 ng/ml separately to the mixture of effector and prelabeled target cells did not produce any significant immunoregulatory effects on NK cell activity against either target. However, cortisol or env-gag at concentrations that did not produce any inhibitory effect on NK activity when used separately, manifested significant inhibitory effects when added in combination. Suppression was evident at concentrations as low as 1 ng/ml of env-gag and 0.05 μg/ml of cortisol and was observed at different effector:target cell ratios. Suppression was not caused by nonspecific toxicity of cortisol or HIV peptides when added in combination to the effector cells nor was due to decreased susceptibility of targets to lysis by effector cells. A non-HIV viral antigen (Rubeola virus) and another HIV-1 envelope-derived sequence (env 578-608 aa) were used as controls separately or in combination with cortisol and did not produce significant inhibition thus demonstrating the specificity of env-gag-induced inhibition. The synergistic inhibitory effect of cortisol-and HIV-derived soluble products in patients with HIV infections are consistent with a model that proposes that stress and circulating HIV-1-derived products may be involved in the progression of HIV infections.