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

Abstract

Treatment of multiple sclerosis (MS) with interferon beta (IFNβ) reduces relapse rate, magnetic resonance imaging (MRI) activity and progression of disability. It has been suggested that this beneficial effect is paralleled by an inhibition of proinflammatory cytokines such as interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) and an induction of anti-inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10). In this study, we record a reduced number of spontaneously IFNγ mRNA-expressing cerebrospinal fluid mononuclear cells (CSF-MC) and IFNγ, TNFα and IL-10 mRNA-expressing peripheral blood mononuclear cells (PBMC) after 6 months of IFNβ-1a treatment, paralleled by a decreased purified protein derivate (PPD)-stimulated and unstimulated IFNγ secretion by PBMC. These effects were not apparent after 2 weeks of treatment, and IFNβ-1a induced IFNγ production by naive PBMC in vitro. We did not record increased numbers of IL-4 mRNA-expressing CSF-MC or PBMC, increased plasma IL-10 levels, increased numbers of IgG, A or M secreting plasma cells or in vitro induction of IL-10 production by IFNβ-1a. We conclude that long-term cytokine modulation by IFNβ-1a differs from acute effects and that downregulation of both pro- and anti-inflammatory cytokines, rather than a shift in the cytokine profile, is apparent after 6 months of IFNβ-1a treatment of MS patients.