Suppression of IL-4 Production in Murine Lymphocytes by Orally Effective Prostaglandin E(1) Analogs

Prostaglandins (PGs) regulate a wide variety of immunologic processes. We studied the activity of PGE(1), and two orally effective PGE(1) methyl ester analogs, misoprostol (MP) and enisoprost (EP), as inhibitors of interleukin-4 (IL-4) production in stimulated murine splenic T cells in vitro. Effective suppresion of IL-4 production was seen with all three agents with KI(50)s of 65 nM for MP and 20 nM for EP. IL-4 is primarily a product of type 2 T helper cells (Th2 cells) and plays an important role in regulating the biosynthesis of immunoglobulins, especially IgE. These in vitro studies, taken together with the recent data of others on modulation of IgE responses by EP and MP in immunized mice in vivo, suggest a possible role for these PGE(1) analogs in the treatment of IgE-mediated diseases in humans.