A POSSIBLE ROLE OF GLUCOCORTICOIDS: AN INTRINSIC INHIBITOR OF THE CYTOTOXIC ACTIVITY OF TUMOR NECROSIS FACTOR

The cytotoxic activity of tumor necrosis factor (TNF) against L929 fibroblasts in vivo was non‐competitively inhibited by physiological concentrations of glucocorticoids such as hydrocortisone (10(‐7)M), corticosterone (5 × 10(‐8)M) and dexamethasone (5 × 10(‐9)M). The inhibition was abolished by the addition of actinomycin D (0.5 μg/ml) or cycloheximide (4μM). A phospholipase A(2) inhibitor, quinacrine (2 × 10(‐6)M), also inhibited the TNF cytotoxicity. These findings suggest that the antitumor cytotoxic reaction by TNF is regulated by glucocorticoid through some mechanism involving de novo transcription and translation and that this regulatory mechanism may involve inhibition of phospholipase A(2) activity.