INTERFERON-BETA-1-B (IFN-B) DECREASES INDUCED NITRIC-OXIDE (NO) PRODUCTION BY A HUMAN ASTROCYTOMA CELL-LINE

Inducible nitric oxide synthase (iNOS) is expressed by astrocytes in d emyelinating regions of multiple sclerosis (MS) brain plaques, suggest ing that NO contributes to MS pathology. Since the immunosuppressive c ytokine IFN-B ameliorates MS disease activity, it is of interest to as sess the modulatory role of IFN-B on NO production. We studied the eff ects of IFN-B, as well as: dexamethasone, IL-10, and transforming grow th factor-beta (TGF-B), on cytokine-induced NO production by the human astrocytoma cell line, A172. L-NMMA and aminoguanidine, competitive i nhibitors of iNOS, suppressed NO production as measured by the NO bypr oduct, nitrite, as did IFN-B. Dexamethasone enhanced NO production, an d IFN-B decreased the amount of this enhancement. Neither IL-10 nor TG F-B inhibited nitrite production. The therapeutic effect of IFN-B in M S may be partly due to suppression of pathogenic NO production. (C) 19 98 Elsevier Science B.V.