title: IFN-gamma, IFN-beta, and PGE1 affect monokine secretion: relevance to monocyte activation in multiple sclerosis.
abstract: Activated antigen-presenting cells and central nervous system microglia produce IL-1 beta, TNF-alpha, IL-6, and PGE-1. These monokines participate in the lymphocyte activation, demyelination, and intrathecal immunoglobulin synthesis seen in multiple sclerosis (MS). Exacerbations of MS are ameliorated by IFN-beta, but provoked by IFN-gamma, possibly through an effect on monocytes (Mo). We studied the effects of IFNs and PG on monokine secretion under stringent low-endotoxin conditions. Spontaneous and IFN-gamma-induced IL-1 beta secretion was greater in MS than in NL Mo. IFN-beta did not inhibit IFN-gamma-induced secretion of monokines, which contrasts with IFN-beta's inhibitory effect on IFN-gamma-induced MHC class II expression. PGE1, a cAMP agonist, caused a 30-fold induction of IL-6 secretion. Indomethacin directly inhibited this induction. Low-dose IFN-beta, through effects on T cells, and cAMP agonists, through effects in T cells and Mo, may ameliorate inflammatory diseases characterized by excessive monokine secretion.
authors.affiliation: Department of Neurology, University of Chicago, Illinois 60637.
authors.forename: A M
authors.initials: AM
authors.lastname: Porrini
authors.forename: A T
authors.initials: AT
authors.lastname: Reder
mesh_terms: D000527:Alprostadil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000276:immunology*; D012636:Secretory Rate / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma; D000527:Alprostadil; D007213:Indomethacin