INFLUENCE OF IFN-BETA-1B (BETAFERON) ON CYTOKINE MESSENGER-RNA 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 cha racteristic for multiple sclerosis (MS). Treatment with interferon-bet a 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 hybr idization with synthetic oligonucleotide probes to detect and enumerat e IFN-gamma, TNF-alpha, IL-10, TGF-beta and perforin mRNA expressing c ells in MS patients before treatment with IFN-beta 1b and during treat ment for 3-6 weeks and for 3-6 months. Numbers of blood MNC spontaneou sly 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 exp ressing MNC were not affected by treatment. IFN-beta 1b had no influen ce 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 m onths 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 a fter 3-6 months of treatment. The results suggest that IFN-beta 1b tre atment upregulates plasma levels of sVCAM-1, but has little effects on numbers of blood MNC expressing mRNA of the pro- and anti-inflammator y cytokines under study. (C) 1998 Lippincott-Raven Publishers.