MODULATION OF MACROPHAGE ACTIVATION BY PROSTAGLANDINS

The effect of prostaglandin E(2), iloprost and cAMP on both nitric oxi de and tumour necrosis factor-alpha release in J774 macrophages has be en studied. Both prostaglandin E(2) and iloprost inhibited, in a conce ntration-dependent fashion the lipopolysaccharide-induced generation o f nitric oxide and tumour necrosis factor-alpha. The inhibitory effect of these prostanoids seems to be mediated by an increase of the secon d messenger cAMP since it was mimicked by dibutyryl cAMP and potentiat ed by the selective type IV phosphodiesterase inhibitor RO-20-1724. Ou r results suggest that the inhibition of nitric oxide release by prost aglandin E(2) and iloprost in lipopolysaccharide-activated J774 macrop hages may be secondary to the inhibition of tumour necrosis factor-alp ha generation, which in turn is likely to be mediated by cAMP.