Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production

J Exp Med. 1995 Feb 1;181(2):775-9. doi: 10.1084/jem.181.2.775.


During human immunodeficiency virus infection and allergic diseases, characterized by a dominant T helper (Th) 2 response, overproduction of prostaglandin E2 (PGE2) is observed. In this paper we studied the effect of PGE2 on interleukin (IL)-12 synthesis, because this cytokine has 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 production, whereas IL-6 production was only partially inhibited by PGE2. In contrast, the production of IL-10 was approximately twofold enhanced at these conditions. The effects of PGE2 were due to its cAMP-inducing capacity, since they could be mimicked by other cAMP inducers. Recombinant 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-10 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 either a Th1 or Th2 response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology
  • Dinoprostone / pharmacology*
  • Humans
  • In Vitro Techniques
  • Interleukin-10 / biosynthesis
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides / pharmacology


  • Interleukin-6
  • Lipopolysaccharides
  • Interleukin-10
  • Interleukin-12
  • Cyclic AMP
  • Dinoprostone