MODULATION OF HELPER T-CELL FUNCTION BY PROSTAGLANDINS

Objective. To determine the influence of prostaglandins on the production of interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5), interferon-gamma (IFN gamma), granulocyte-macrophage colony-stimulating factor, and transforming growth factor beta 1 by CD4+ T cells. Methods. TH0, TH1, and TH2 T cell clones were stimulated in the presence and absence of the prostaglandin E(2) (PGE(2)) analog misoprostol and PGE(2). Lymphokine production was analyzed by using a semiquantitative polymerase chain reaction with lymphokine-specific primer sets and/or by determining lymphokine activity in bioassays. Results. PGE(2) and misoprostol have distinct effects on different functional T helper cells. TH1 cells, which predominantly produce IL-2 and IFN gamma, are completely inhibited, while TH2 cells, which preferentially produce IL-4 and IL-5, are largely unaffected. Misoprostol and PGE(2) are equivalent in their ability to modulate T cell function. In the presence of prostaglandins, THO-like helper cells, which are characterized by the coproduction of multiple lymphokines, function as TH2 cells; however, they do not differentiate into TH2 T cells. Conclusion. Prostaglandins that are produced in inflamed tissue can regulate the functional capabilities of infiltrating T cells. In the presence of PGE(2), TH1-like responses are suppressed and THO-like responses are shifted toward a TH2-like pattern dominated by the production of IL-4 and IL-5. Inhibition of prostaglandin production by antiinflammatory agents might restore TH1 responses with local production of IL-2 and IFN gamma.