Inhibition of cytotoxic responses by prostaglandin E 2 in the presence of interleukin 2

Abstract

Experiments are described which provide direct evidence for a strong suppressive effect of prostaglandin E 2 (PGE 2) on the activation of cytotoxic T lymphocytes (CTL). The experiments also tested the hypothesis that PGE 2 inhibits cytotoxic responses exclusively by preventing the helper T cells from producing interleukin 2 (IL-2). In support of this hypothesis we found that indomethacin enhanced cytotoxic responses in the absence but not in the presence of concanavalin A-activated spleen cell supernatant (CSCS) indicating that the endogenously produced prostaglandin(s) inhibited primarily the production of IL-2. However, the addition of PGE 2 to microcultures was found to inhibit in a dose-dependent manner the activation of cytotoxic responses against I-region compatible stimulator cells even in the presence of CSCS. This inhibition was not observed in the presence of I-region incompatible stimulator cells, indicating that the inhibitory effect of PGE 2 did not result from a general toxic effect on the culture. The results argue against the notion that PGE 2 inhibits cytotoxic responses exclusively by preventing the production of IL-2.