Mechanism of glucocorticoid action on murine natural killer cell activity.

With the use of an in vitro model system, the mode of action of glucocorticoids on murine natural killer (NK) cell-mediated cytotoxicity of tumor cells was investigated. Of the steroids tested, only the glucocorticoids notably suppressed NK activity. Glucocorticoids were not toxic to the NK effector cell since inhibitors of protein synthesis protected NK activity from the suppressive action of glucocorticoids. Glucocorticoid-treated C57BL/6J spleen cells, although suppressed in NK activity, were unable to suppress the NK activity of normal syngeneic spleen cell cultures. Similarly, the supernatants of glucocorticoid-treated cultures were also unable to suppress normal NK activity. Thus a role for suppressor cell activity or soluble suppressive factors was excluded. Results of analyses of the NK activity of Percoll-fractionated glucocorticoid-treated C3H/HeN (nu/nu) spleen cells at the single-cell level demonstrated that NK effector cells could efficiently bind to YAC-1 lymphoma cells but were incapable of inducing cytolysis. Moreover, the production of NK cytotoxicity factor(s) in tumor cell-stimulated nude mouse spleen cell cultures was severely depressed after glucocorticoid treatment. The results of these studies suggest that glucocorticoids suppress murine NK activity by acting directly on the NK effector cells, possibly by inhibiting the formation or release of specific effector molecules that are cytotoxic to NK-sensitive tumor cells.