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

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 PGE2 with an I50 of 2 nM. Comparable suppression by PGE2 was seen after priming by anti-CD3 epsilon antibody instead of Con A or with other changes in the culture conditions. PGE2 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 microM indomethacin, indicating that endogenous arachidonate metabolites such as PGE2 and PGI2 regulate IL-4 production in our usual culture system. The inhibition of Th2 cell secretion by PGE2 in vitro may have physiologic and pharmacologic implications for the regulation of Th2 cell function and IgE production in vivo.