title: Prostaglandin E2 inhibits the release of tumor necrosis factor-alpha, rather than interleukin 1 beta, from human macrophages.
abstract: We have reported previously that macrophages obtained from renal patients on continuous ambulatory peritoneal dialysis (CAPD) during an episode of infectious peritonitis display a decrease in intracellular cAMP levels and in spontaneous in vitro release of PGE2 and PGI2. Such macrophages also release large quantities of IL-1 beta and TNF alpha when stimulated in vitro by LPS. In view of the interregulatory effects between PGE2 and macrophage cytokines (IL-1 beta and TNF alpha) in their production, we examined in the present work to what extent the LPS-induced release of either IL-1 beta or TNF alpha in vitro from CAPD-originated peritoneal macrophages is affected by graded doses of exogenous PGE2 (range 0-1000 ng/ml) and by the cyclooxygenase inhibitor indomethacin (INDO) (10(-6) M). IL-1 beta and TNF alpha were determined using an enzyme-linked immunoabsorbent assay and an immunoradiometric assay, respectively. We found that PGE2 invariably induced a dose-dependent decrease in TNF alpha release. In peritoneal macrophages collected during an infection-free period, TNF alpha release decreased from 3225 pg/ml (controls) to 353 pg/ml at 1000 ng/ml of PGE2, and in peritoneal macrophages collected during an episode of infectious peritonitis, it decreased from 4100 pg/ml (controls) to 545 pg/ml at 100 ng/ml of PGE2. However, PGE2 failed to influence the secretion of IL-1 beta. INDO induced an approx. two-fold increase in TNF alpha release, but had no effect on IL-1 beta release. These findings indicate that exogenous and endogenous PGE2 controls the release of TNF alpha rather than IL-1 beta from LPS-stimulated peritoneal macrophages.
authors.affiliation: Department of Internal Medicine I, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: Fieren
authors.forename: G J
authors.initials: GJ
authors.lastname: van den Bemd
authors.forename: S
authors.initials: S
authors.lastname: Ben-Efraim
authors.forename: I L
authors.initials: IL
authors.lastname: Bonta
mesh_terms: D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects; D010538:Peritonitis / Q000276:immunology*; D011863:Radioimmunoassay; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D007213:Indomethacin