Prostaglandin E synthesis and release by murine macrophages and human monocytes after in vitro treatment with biological response modifiers.
Prostaglandins of the E series (PGE), produced by mononuclear phagocytes, have many biological activities and are involved in the regulation of myelopoiesis and of the cytotoxic activities of macrophage (M phi) and natural killer (NK) cells. Since one of the possible effects of biological response modifiers (BRMs) on immune regulation might be modulation of PGE production, resident peritoneal murine M phi (mM phi) and elutriated human blood monocytes (hM) were incubated with BRMs and the supernatants were then assayed for PGE. Control mM phi produced about 4.9 ng PGE/10(5) mM phi over a 24 hr period. Lipopolysaccharide (LPS, 1-5 micrograms/ml), polyinosinic-polycytidylic acid complexed with poly-L-lysine (Poly ICLC, 0.1-10 micrograms/ml) and murine alpha, beta-interferon, (IFN, 10-1000 U/ml) all caused a highly significant increase in PGE-secretion. BM41.332, a 2-cyanoaziridine (25-50 micrograms/ml), was found to be less stimulatory, whereas the pyran copolymer MVE-2 (25-50 micrograms/ml), and Azimexone (25-50 micrograms/ml) had marginal effects on PGE-production. Kinetic studies showed that the plateau of PGE-production by mM phi occurred during the first 24 hr of incubation, and mM phi which were washed after a 24 hr incubation period could not be restimulated to produce more PGE. PGE release by hM was increased after stimulation with LPS, Poly IGLC and BM41.332, whereas human IFNs (alpha and beta) induced a slight decrease in PGE production. As in the murine studies, Azimexone and MVE-2 had no detectable effect. The ability of some BRMs to augment PGE-secretion by mM phi and hM may contribute to their negative effects on host responses, such as suppression of NK cell activity.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001388:Aziridines / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008299:Maleic Anhydrides / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D001388:Aziridines; D008070:Lipopolysaccharides; D008299:Maleic Anhydrides; D011458:Prostaglandins E; C035520:ciamexon; C016866:azimexon; D007372:Interferons; D011070:Poly I-C