UCL Discovery

Abstract

Background Subcutaneous IFN beta-lb (Betaferon(R)) is an established immunomodulatory treatment for relapsing remitting MS and active secondary progressive multiple sclerosis (SPMS). It modulates cytokine and adhesion molecule expression but long term in vivo effects of IFN beta-Ib on the immune system are not known in multiple sclerosis. Objective To address the effects of IFN beta-lb on serum levels for soluble adhesion molecules and cytokine receptors from MS patients. Methods Serial blood samples were obtained from 40 patients of the frequent MRI subgroup (20 patients each from the placebo and the IFN beta-lb treatment group), participating in the European multi-center clinical trial with IFN beta- lb for secondary progressive MS, at regular intervals for up to 36 months. Soluble adhesion molecules (sVCAM, sICAM- 1, sL-Selectin) as well as TNF-receptor I and 11 were analysed in the serum of patients by enzyme linked immunosorbent assays (ELISAs). Monthly brain MRI was performed in 34 of these patients (16 patients from the placebo and 18 from the IFN beta-Ib group) during months 1-6 and 19-24 to monitor disease activity as assessed by newly occurring gadolinium (Gd) enhancing lesions. Results An early and significant increase in sVCAM and sTNF-RII serum levels was detected in 16 out of 20 patients (80 %) treated with subcutaneous IFN beta-lb already at month I but was absent in all but one patient during placebo treatment (p < 0.0 1). Raised sVCAM and TNF RII serum levels during months 1-6 inversely correlated with less MRI activity in the 19-24 months treatment interval in the IFN beta-lb treatment group ( p = 0.0093 for TNF-RII; p = 0.047 for VCAM). Conclusions sVCAM and sTNF RII levels in the serum of SPMS patients are increased during IFN beta-lb therapy and may at least in part explain some of the treatment effects, like reduced immune cell transmigration.