Modulation of IL-4 production in murine spleen cells by prostaglandins

Abstract

Recently, it has been reported that IL-4 production by murine Th2 cell lines is insensitive to inhibition by E-type prostaglandins. In the present study, IL-4 production in vitro by freshly isolated concanavalin A (Con A)-stimulated murine spleen cells was readily suppressed by PGE 2 with an I 50 of 2 n M. Comparable suppression by PGE 2 was seen after priming by anti-CD3ϵ antibody instead of Con A or with other changes in the culture conditions. PGE 2 was an effective inhibitor after elimination of Ly2.2 + T cells, consistent with a direct effect on Th2 cells. In the absence of added prostaglandins, IL-4 production was enhanced 1.5- to 7.0-fold by 0.2–2.0 μ M indomethacin, indicating that endogenous arachidonate metabolites such as PGE 2 and PGI 2 regulate IL-4 production in our usual culture system. The inhibition of Th2 cell secretion by PGE 2 in vitro may have physiologic and pharmacologic implications for the regulation of Th2 cell function and IgE production in vivo.