DEXAMETHASONE INHIBITS IL-1 AND TNF ACTIVITY IN HUMAN LUNG FIBROBLASTS WITHOUT AFFECTING IL-1 OR TNF RECEPTORS

Interleukin (IL-1) and tumor necrosis factor (TNF) activate human lung fibroblasts through interactions with specific receptors. One effect of this interaction of IL-1 and TNF with fibroblasts is an increased p roduction of the cytokines, IL-6 and IL-8. Dexamethasone blocks the in duction of IL-6 and IL-8 by IL-1 or TNF. In these studies, we determin ed whether dexamethasone interferes with the upregulation of IL-6 and IL-8 by downregulating expression of the IL-1 or TNF receptor genes. C onfluent lung fibroblasts were treated with medium alone (control) or medium with dexamethasone (10(-6) M). Dexamethasone did not decrease t he binding of IL-1 and TNF to their receptors, nor did it decrease amo unts of IL-1 or TNF receptor RNA. Both IL-1 and TNF increased release of IL-6 and IL-8 from the cells in a dose-dependent manner and dexamet hasone inhibited this effect. Dexamethasone also inhibited the inducti on of IL-6 and IL-8 RNA by IL-1 and TNF. The studies show that dexamet hasone does not block the effects of IL-1 or TNF on fibroblasts by dec reasing expression of IL-1 or TNF receptors.