Regulation of interleukin 1 production by mouse peritoneal macrophages. Effects of arachidonic acid metabolites, cyclic nucleotides, and interferons.
The effects of prostaglandin E2 (PGE2), cyclic nucleotides, leukotriene B4 (LTB4), and interferons on interleukin 1 (IL 1) production by lipopolysaccharide (LPS)-stimulated C3H/HeNCrl mouse peritoneal macrophages were studied. IL 1 production was inhibited by PGE2, the adenosine 3':5'-monophosphate analog dibutyryl cAMP, the cAMP agonist isoproterenol, and the phosphodiesterase inhibitor isobutylmethylxanthine. These agents were more inhibitory when added early in the latent phase of IL 1 synthesis following stimulation with LPS rather than just prior to release of IL 1 into the medium. Production of both the intracellular and extracellular forms of IL 1 was blocked by PGE2 and cAMP. Suppression of LPS-induced IL 1 production by PGE2 was prevented by leukocyte alpha-interferon. Moreover, alpha-interferon augmented LPS-induced IL 1 production but did not stimulate IL 1 production in the absence of LPS. Immune gamma-interferon markedly inhibited LPS-stimulated IL 1 production. The lipoxygenase inhibitor eicosa-5,8,11,14-tetraynoic acid suppressed, whereas 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline augmented, LPS-induced IL 1 production. The opposing effects of these agents suggested that lipoxygenase metabolites do not act as inducers of IL 1 production. Purified LTB4 did not stimulate base-line or augment LPS-induced IL 1 production (both intracellular and extracellular forms). Moreover, calcium ionophore A23187 (a lipoxygenase activator) did not stimulate IL 1 production, alone or in combination with LTB4. Thus, net IL 1 production by macrophages may be regulated by a balance between the effects of PGE2, cAMP, alpha-interferon, and gamma-interferon, but not LTB4.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008555:Melitten / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D011458:Prostaglandins E / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives*
D001095:Arachidonic Acids; D007375:Interleukin-1; D011458:Prostaglandins E; D008555:Melitten; D003994:Bucladesine; D007371:Interferon-gamma; D013806:Theophylline; D015232:Dinoprostone; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin