Regulation of thymocyte proliferative response by macrophage‐derived prostaglandin E2 and inter leukin 1

The antagonistic effects of macrophage (MΦ)-derived interleukin 1 (IL1) and prostaglandin Ez (PGE2) on thymocyte proliferation were uncoupled and studied. Elimination of PGE2 from the culture medium of prostaglandin Ez-stimulated MΦ was achieved by dialysis of the media or by indomethacin treatment of the Ma. IL1 secretion appears to be PGE2 independent. Experiments using exogenous PGEzrevealed a quantitative relationship between the two monokines. PGE2 (1.25 ng/ml) reduced the proliferative effect of IL 1 produced by 1.5 × 105 peritoneal MQ, to 50%. This PGE2 dose increased significantly the levels of intracellular cAMP. Separation of peritoneal exudate MΦ on a bovine serum albumin discontinuous gradient demonstrated that the main part of PGE2 synthesis was in a fraction of lower density, large MΦ, whereas IL1 activity was detected in all tested fractions.