Differential response to dexamethasone on the TXB(2) release in guinea-pig alveolar macrophages induced by zymosan and cytokines

Glucocorticosteroids reduce the production of inflammatory mediators but this effect may depend on the stimulus. We have compared the time course of the effect of dexamethasone on the thromboxane B(2) (TXB(2)) release induced by cytokine stimulation and zymosan in guinea-pig alveolar macrophages. Interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and opsonized zymosan (OZ), all stimulate TXB(2) release. High concentrations of dexamethasone (1–10 μM) inhibit the TXB(2) production induced by both cytokines and OZ, but the time course of this response is different. Four hours of incubation with dexamethasone reduce the basal TXB(2) release and that induced by IL-1β and TNF-α, but do not modify the TXB(2) release induced by OZ. However, this stimulus was reduced after 24 h incubation. Our results suggest that the antiinflammatory activity of glucocorticosteroids shows some dependence on stimulus and, therefore, may have more than one mechanism involved.