EFFECTS OF PROSTAGLANDINS AND CYCLIC-AMP ON CYTOKINE PRODUCTION IN RAT LEUKOCYTES

Prostaglandins E(1), prostaglandin E(2), 3-oxa-methano-prostaglandin I -1 (SM-10906), a stable prostaglandin I-2 analog, and dibutyryl cyclic AMP suppressed the production of tumor necrosis factor and interleuki n-l in lipopolysaccharide-stimulated rat pleural resident monocytic ce lls, whereas they enhanced the production of interleukin-6 and cytokin e-induced neutrophil chemoattractant (CINC), a rat interleukin-8-like chemokine, in these cells. SM-10906 also inhibited the in vivo product ion of tumor necrosis factor and interleukin-l in pleural exudates, wh en injected into the rat pleural cavity concomitantly with carrageenin . The cyclic AMP (cAMP) level in the lipopolysaccharide-stimulated res ident cells was increased when the cells were incubated in the presenc e of prostaglandin E(1), prostaglandin E(2) or SM-10906. Prostaglandin I-2 showed only slight effects. The addition of pentoxifylline, a pho sphodiesterase inhibitor, to the incubation mixture increased the cAMP level and also enhanced the effect of prostaglandins, indicating that these regulating actions of prostaglandins may be exerted partly thro ugh a mechanism involving an increased intracellular cAMP level.