Effect of cortisol on the native and in vitro induced non-MHC restricted cytotoxicity of large granular lymphocytes.

Natural Killer (NK) activity has been shown to be depressed under stressful conditions. Glucocorticoids, which are known to increase during stress, seem to negatively regulate the activity of NK cells. In the present study we have explored the effect of cortisol (hydrocortisone, HC) on NK activity. A significant inhibitory effect could be observed as early as 6 hr after the addition of HC at the concentration of 0.5 microM, corresponding to the upper physiological circulating level. Both the lysis and the binding of the K562 target cells were affected by HC, indicating that the hormone acts on the target recognition phase. The HC-mediated inhibition of the NK activity was fully reversed after 6 hr incubation in a HC-free medium. The observation of comparable levels of NK-inhibition using unseparated PBL or purified LGL, show that HC acts directly on LGL to inhibit their cytotoxic function. The effect of HC on the responsiveness of NK cells to the modifiers beta-interferon (beta-IFN) and recombinant interleukin 2 (rIL2) was also studied. Pre-incubation with HC did not alter the enhancement of the activity induced by beta-IFN, demonstrating that the HC- and beta-IFN-mediated effects occur in separate NK subsets. By contrast the increase of NK cytotoxicity induced by rIL2 was lower in the HC-treated compared to the untreated cell cultures (35.8 +/- 6.2 and 20.7 +/- 4.3% respectively, p less than 0.05) which could indicate that a portion of the cells triggered by rIL2 belong to the HC-sensitive NK subpopulation.