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

Abstract

SummaryDuring 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 Thl 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 cAMPinducing 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-IO 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 Thl or Th2 response.

Prostaglandin E2 down-regulates viable Bacille Calmette–Guérin-induced macrophage cytotoxicity against murine bladder cancer cell MBT-2in vitro

“…Furthermore, it was reported that PGE 2 was a potent inhibitor of IL-12 production [21,22]. In our study, IL-12 production by BCG-treated macrophages was down-regulated by exogenous PGE 2 as well as IFN-g and TNF-a, but not enhanced by COX inhibitors (data not shown).…”

Microbial Compounds Selectively Induce Th1 Cell-Promoting or Th2 Cell-Promoting Dendritic Cells In Vitro with Diverse Th Cell-Polarizing Signals

“…So far, little is known about the molecular cross-talk between DCs and pathogens. The capability of CT and PGE 2 to prime for DC2s can be attributed to their ability to enhance the levels of intracellular cAMP, which block the development of IL-12 responses (27). CT signaling, however, differs from PGE 2 signaling in that PGE 2 by itself is unable to induce maturation (11), whereas CT does induce maturation (4), although not always completely (data not shown).…”

IL‐10 Plays a Role in the Modulation of Human Granulomatous Hypersensitivity Against Schistosoma mansoni Eggs Induced by Immune Complexes

“…Kambayashi et al [27] have shown in murine model that tumour-derived PGE 2 prevents tumour-infiltrating macrophages from producing TNF-a, in part by augmenting macrophage IL-10 synthesis. Also van der Pouw Kraan et al [28] in studies in human immunodeficiency virus infection and in allergic reactions have detected an overproduction of PGE 2 . This mediator induces a twofold enhancement in IL-10 production and seems to play an important role in the development of either a Th1 or Th2 response.…”