Influence of IFN-β1b (Betaferon) on cytokine mRNA profiles in blood mononuclear cells and plasma levels of soluble VCAM-1 in multiple sclerosis

Inflammatory cell infiltration within the central nervous system (CNS) and upregulation of both pro- and anti-inflammatory cytokines are characteristic for multiple sclerosis (MS). Treatment with interferon-beta 1b (IFN-beta 1b) reduces the number and severity of MS relapses. To examine whether treatment with IFN-beta 1b affects levels of cytokine mRNA expressing blood mononuclear cells (MNC) we employed in-situ hybridization with synthetic oligonucleotide probes to detect and enumerate IFN-gamma, TNF-alpha, IL-10, TGF-beta and perforin mRNA expressing cells in MS patients before treatment with IFN-beta 1b and during treatment for 3-6 weeks and for 3-6 months. Numbers of blood MNC spontaneously expressing TNF-alpha and IL-10 mRNA were lower after 3-6 months of treatment, while numbers of IFN-gamma, TGF-beta and perforin mRNA expressing MNC were not affected by treatment. IFN-beta 1b had no influence on levels of MBP-reactive IFN-gamma, TNF-alpha, TGF-beta, IL-10 or perforin mRNA expressing blood MNC determined after 3-6 weeks or 3-6 months of treatment. Parallel measurements of plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) revealed elevated levels after 3-6 weeks of treatment and these levels remained higher after 3-6 months of treatment. The results suggest that IFN-beta 1b treatment upregulates plasma levels of sVCAM-1, but has little effects on numbers of blood MNC expressing mRNA of the pro- and anti-inflammatory cytokines under study. (C) 1998 Lippincott-Raven Publishers.