Induction of serum soluble tumor necrosis factor receptor II (sTNF-RII) and interleukin-1 receptor antagonist (IL-1ra) by interferon beta-1b in patients with progressive multiple sclerosis

Background Cytokine inhibitors, such as soluble tumor necrosis factor receptor II (sTNF-RII) and interieukin-1 receptor antagonist (IL-1ra) are possible regulators of proinflammatory cytokine activity. Although previous studies have shown induction of sTNF-RII and IL-1ra by interferon-beta (IFN) in patients with relapse-onset forms of multiple sclerosis (NIS), to date no studies of these cytokine inhibitors have been performed in patients with essentially progressive forms of MS. Objective To address the effects of IFN on serum levels of sTNF-RII and IL-1ra in a cohort of progressive NIS patients and to assess the relationship between levels and changes of sTNF-RII and IL-1ra and clinical and radiological variables. Methods Serial blood samples were obtained from a cohort of 73 patients with progressive MS who participated in a placebo-controlled clinical trial with IFN beta-1b. Serum levels of sTNF-RII and IL-1ra were measured by multiplex enzyme-linked immunosorbent assay at baseline and after 3,6,12, and 24 months. EDSS and MSFC scores were recorded at the time of bloodsampling, and MR scans were obtained at baseline and after 12 and 24 months. Results Treatment with IFN beta was associated with significant increases of sTNF-RII and IL-1ra serum levels during the follow-up period. A strong correlation at 24 months was observed between levels of sTNF-RII and EDSS scores in the placebo group. Finally, a trend for negative association was found between changes in sTNF-RII and percentage change in T2-weighted lesion load at 24 months in the IFN beta treated group. Conclusions sTNF-RII and IL-1ra levels are increased in the serum of progressive MS patients during IFN beta therapy and may be one mechanism by which IFN beta mediates its effects in the treatment of MS.