Regulation of thymocyte proliferative response by macrophage-derived prostaglandin E2 and interleukin 1.

The antagonistic effects of macrophage (M phi)-derived interleukin 1 (IL 1) and prostaglandin E2 (PGE2) on thymocyte proliferation were uncoupled and studied. Elimination of PGE2 from the culture medium of prostaglandin E2-stimulated M phi was achieved by dialysis of the media or by indomethacin treatment of the M phi. IL1 secretion appears to be PGE2 independent. Experiments using exogenous PGE2 revealed a quantitative relationship between the two monokines. PGE2 (1.25 ng/ml) reduced the proliferative effect of IL 1 produced by 1.5 X 10(5) peritoneal M phi to 50%. This PGE2 dose increased significantly the levels of intracellular cAMP. Separation of peritoneal exudate M phi on a bovine serum albumin discontinuous gradient demonstrated that the main part of PGE2 synthesis was in a fraction of lower density, large M phi, whereas IL 1 activity was detected in all tested fractions.