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Direct Suppression of Natural Killer Activity in Human Peripheral Blood Leukocyte Cultures by Glucocorticoids and Its Modulation by Interferon¹

Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03756 [N. J. H., H. C. H.], and Department of Medical Microbiology and Immunology, University of South Florida Medical Center, Tampa, Florida 33612 [W. I. C.]

In vitro treatment of human peripheral blood leukocytes for 18 to 24 hr with physiological concentrations of glucocorticoids resulted in a marked decrease (up to 90%) in natural killer (NK) activity. The effect on NK activity was both dose and time dependent and was specific for glucocorticoids. Glucocorticoids had no effect when added directly to the 4-hr ⁵¹Cr release cytotoxicity assay, nor did they alter the susceptibility of K562 cells to NK-mediated cytolysis. Glucocorticoid-induced inhibition occurred in Percoll-fractionated peripheral blood leukocytes enriched for NK activity. Viabilities of steroid-treated and untreated cultures were similar. Mixing experiments failed to demonstrate the involvement of suppressor activity in the inhibition. Purified cloned human leukocyte interferon subtype A and inducers of interferon enhanced NK activity in the presence of glucocorticoid, although the levels of enhancement were lower than those produced by these agents in the absence of the steroid.

Thus, glucocorticoids appear to suppress human NK activity by interacting directly with the NK effector cell, and our results obtained with physiological concentrations of these steroids suggest that they may play an important role in regulating NK activity in vivo. Additionally, these findings suggest a possible means for overriding this immunosuppressive side effect of glucocorticoid therapy by simultaneous treatment with interferon.

¹ This research was supported by Research Grants CA 17323 and AM 03535 and by Cancer Center Core Grant CA 23108 from the USPHS.

² Supported during part of these studies by National Service Award CA 09367 and currently by a fellowship awarded by the Leukemia Society of America. Present address: Laboratory of Pathology, NIH, Bethesda, Md. 20205. To whom requests for reprints should be addressed.

Received 1/27/83. Accepted 5/26/83.

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