REGULATION BY PGE(2) OF IL-2, IL-3 AND IFN PRODUCTION BY CORTICO-RESISTANT THYMOCYTES

We have investigated the role of prostaglandin E(2) (PGE(2)) in the regulation of cytokine release (IL-2, IL-3 and IFN) by cortico-resistant thymocytes (CRT) stimulated or not through the T-cell antigen receptor by an anti-CD3 monoclonal antibody (mAb). CRT were found to spontaneously produce IL-2 and IL-3 on day 4 of culture, but not IFN. After activation with an anti-CD3 mAb, the maximal levels for IL-2 and IFN were observed on day 1 and for IL-3 on day 4. Addition of PGE(2) inhibits IL-2 production and has no effect on IFN production. Indomethacin, an inhibitor of the cyclooxygenase pathway, enhanced both IL-2 and IFN production. In contrast, IL-3 secretion by anti-CD3 activated CRT was upregulated by PGE(2), and its level was decreased in the presence of indomethacin in both stimulated or unstimulated cells. As has been observed with PGE(2), forskolin which activates adenylate cyclase increases the IL-3 level. Thus PGE(2) may interfere in the process of thymocyte proliferation and/or differentiation by regulating differentially the interleukin production.