Reduction of both pro- and anti-inflammatory cytokines after 6 months of interferon beta-1a treatment of multiple sclerosis

Treatment of multiple sclerosis (MS) with interferon beta (LFN beta) reduce s relapse rate, magnetic resonance imaging (MRI) activity and progression o f disability. It has been suggested that this beneficial effect is parallel ed by an inhibition of proinflammatory cytokines such as interferon gamma ( IFN gamma) and tumor necrosis factor alpha (TNF alpha) and an induction of anti-inflammatory cytokines such as interleukin-4 (IL-4) and winterleukin-1 0 (IL-10). In this study, we record a reduced number of spontaneously IFN g amma mRNA-expressing cerebrospinal fluid mononuclear cells (CSF-MC) and IFN gamma, TNF alpha and IL-10 mRNA-expressing peripheral blood mononuclear ce lls (PBMC) after 6 months of IFN beta-1a treatment. paralleled by a decreas ed purified protein derivate (PPD)-stimulated and unstimulated IFN gamma se cretion by PBMC. These effects were not apparent after weeks of treatment, and IFN beta-1a induced IFN gamma production by naive PBF IC in vitro. We d id not record increased numbers of IL-4 mRNA-expressing CSF-MC or PBMC, inc reased plasma IL-10 levels, increased numbers of IgG, A or M secreting plas ma cells or in vitro induction of IL-10 production by IFN beta-1a. We concl ude that long-term cytokine modulation by IFN beta-1a differs from acute ef fects and that downregulation of both pro- and anti-inflammatory cytokines, rather than a shift in the cytokine profile, is apparent after 6 months of IFN beta-1a treatment of MS patients. (C) 2000 Elsevier Science B.V. All r ights reserved.