IFN-gamma, IFN-beta, and PGE1 affect monokine secretion: relevance to monocyte activation in multiple sclerosis

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.