DIFFERENTIAL RESPONSE TO DEXAMETHASONE ON THE TXB2 RELEASE IN GUINEA-PIG ALVEOLAR MACROPHAGES INDUCED BY ZYMOSAN AND CYTOKINES

Glucocorticosteroids reduce the production of inflammatory mediators b ut this effect may depend on the stimulus. We have compared the time c ourse of the effect of dexamethasone on the thromboxane B-2 (TXB2) rel ease induced by cytokine stimulation and zymosan in guinea-pig alveola r macrophages. Interleukin-1 beta (IL-1 beta) tumour necrosis factor-a lpha (TNF-alpha) and opsonized zymosan (OZ), all stimulate TXB2 releas e. High concentrations of dexamethasone (1-10 mu M) inhibit the TXB2 p roduction induced by both cytokines and OZ, but the time course of thi s response is different. Four hours of incubation with dexamethasone r educe the basal TXB2 release and that induced by IL-1 beta and TNF-alp ha, but do not modify the TXB2 release induced by OZ. However, this st imulus was reduced after 24h incubation. Our results suggest that the antiinflammatory activity of glucocorticosteroids shows some dependenc e on stimulus and, therefore, may have more than one mechanism involve d.