PROSTAGLANDIN-E2 IS A POTENT INHIBITOR OF HUMAN INTERLEUKIN-12 PRODUCTION

During human immunodeficiency virus infection and allergic diseases, c haracterized by a dominant T helper (Th) 2 response, overproduction of prostaglandin E2 (PGE2) is observed. In this paper we studied the eff ect of PGE2 on interleukin (IL)-12 synthesis, because this cytokine ha s been described to be essential in induction of Th1 responses. IL-12 synthesis was induced in monocytes that were stimulated with Neisseria meningitidis-derived lipopolysaccharide in whole blood cultures. PGE2 almost completely inhibited lipopolysaccharide induced IL-12 producti on, whereas IL-6 production was only partially inhibited by PGE2. In c ontrast, the production of IL-10 was approximately twofold enhanced at these conditions. The effects of PGE2 were due to its cAMP-inducing c apacity, since they could be mimicked by other cAMP inducers. Recombin ant human IL-10 also inhibited IL-12 and IL-6 production. However, the inhibitory effect of PGE2 on IL-12 production was independent of IL-1 0 since neutralizing anti-IL-10 antibodies were unable to reverse this inhibition. These results suggest that the capacity of an antigen to induce PGE2 synthesis may play a crucial role in the development of ei ther a Th1 or Th2 response.