DIFFERENTIAL-EFFECTS OF INDOMETHACIN AND DEXAMETHASONE ON CYTOKINE PRODUCTION IN CARRAGEENAN-INDUCED RAT PLEURISY

The effect of anti-inflammatory drugs on cytokine production at local inflammatory sites was investigated in a carrageenin-induced rat pleur isy model. Exudate volume and leukocyte number in the pleural cavity a t 3 h after the carrageenin injection were significantly reduced by th e pretreatment with indomethacin or dexamethasone. Both drugs also red uced the prostaglandin E(2) level in the exudate. However, production of tumor necrosis factor (TNF) and interleukin-1 in the pleural exudat e was significantly enhanced by the pretreatment-with indomethacin, wh ereas the interleukin-6 level was reduced. Pretreatment with dexametha sone markedly suppressed all these cytokine levels. When resident pleu ral cells were stimulated with lipopolysaccharide in vitro, the presen ce of exogenous prostaglandin E(2) reduced the production of TNF and i nterleukin-1, while it increased that of interleukin-6 in a dose-depen dent manner. These results suggest that prostaglandin E(2) could be a regulating factor involved in cytokine production at the inflammatory site. Dexamethasone may express a direct suppressive action on cytokin e production rather than an indirect regulatory action through prostag landin E(2) level.