Direct stimulation of ADCC by cloned gamma interferon is not ablated by glucocorticoids: studies using a human monocyte-like cell line (U-937).

We have used the macrophage-like cell line U-937 to demonstrate that recombinant gamma (immune) interferon (gamma-IFN) acts directly on the mononuclear phagocyte in the absence of other cell types to increase Fc receptor sites and antibody-dependent cellular cytotoxicity (ADCC). Incubation of U-937 for 18 hr with 2% gamma-IFN-rich supernatant, or with 10 U/ml of pure recombinant gamma-IFN, resulted in a seven-fold increase in Fc receptors as measured by the binding of radiolabeled IgG or fluoresceinated IgG and cytofluorography. Simultaneous measurement of ADCC for chick erythrocytes showed a seven-fold increase. This augmentation of Fc receptors and function was not ablated by an immunosuppressive cocn of the glucocorticoid dexamethasone. The potent effects of gamma-IFN both on surface receptors and effector functions of macrophages suggest that it is an important mediator in the efferent limb of immunity. Moreover, our findings that physiologic levels of glucocorticoids do not block activation of the mononuclear phagocyte support our view that glucocorticoids are immunosuppressive as a result of their action on gamma-IFN-producing cells. This would seem an important consideration in the development of potential strategies for obviating steroid-induced immunosuppression.