Infectious-inflammatory changes in cyclic AMP levels and in their regulation by prostaglandins in human peritoneal macrophages

Abstract

Peritoneal macrophages of renal patients on continuous ambulatory peritoneal dialysis (CAPD) have been collected when CAPD was without complications, during an intercurrent infectious peritoneal inflammation and after recovery. Levels of cyclic AMP, release of cyclo-oxygenase metabolites, and responsiveness, in terms of cyclic AMP elevation, to either PGE 2 or to DC-PGI 2 (a stable analogue of PGI2) were examined. Peritoneal. inflammation was associated with a sharp drop in cyclic AMP, which was restored after recovery. Production of TxA 2, PGI 2 and PGE 2 parallelled the direction of changes in cyclic AMP levels, except, that release of PGE 2 entirely failed to recover. Macrophages during the uncomplicated stage of CAPD proved more responsive to DC-PGI 2 than to PGE 2.During inflammation the cells displayed a marked increase in sensitivity towards PG stimulation. Improved sensitivity was more pronounced with PGE 2 than with DC-PGI 2 and so the original difference between responsiveness of the cells to the PGs was abolished. Several findings are compatible with the view that endogenous PGI 2 governs the cyclic AMP levels in human non-inflammatory peritoneal macrophages. However, during infectious-inflammation the cells undergo changes which render a reduced production of PGI2 insufficient to explain the drop in cyclic AMP.