Interleukin-1 receptor antagonist, soluble tumor necrosis factor-a receptor type I and II and soluble E-selectin serum levels in multiple sclerosis patients receiving weekly intramuscular injections of interferon-β1a

Background: interferon beta (IFN-β) reduces relapse rate and disease progression in patients with the relapsing-remitting form of multiple sclerosis (RRMS). IFN-β may act by upregulating the expression of anti-inflammatory components of the immune system. Objectives: To determine whether weekly intramuscular (i.m.) injection of IFN-β1a had a short- or long-term effect on the expression of naturally occurring soluble factors that play an immunosuppressive role within the cytokine network. Materials and Methods: serum levels of interleukin-1 receptor antagonist (IL-1Ra), soluble tumor necrosis factor alpha receptor type I and type II (sTNF-αRI and sTNF-αRII), and soluble E-selectin (sE-Sel) were followed over time in ten patients with RRMS who were treated with weekly i.m. injections of 30 μg (= 6 MU) of IFN-β1a. Patient sera were sampled before, and 24, 48, 72, 96, and 168 hours after the first TFN-β1a injection (short-term), and then at 1, 3, 6, 9 and 12 months after therapy initiation (long-term); highly sensitive, commercially available ELISA tests were used. Results: serum levels of IL-1Ra, sTNF-αRI and sTNF-αRII, but not sE-Sel were significantly increased in both short- and long-term follow-up. Interestingly, IL-1Ra, sTNF-αRI and sTNF-αRII behaviors were completely different, suggesting that these naturally occurring immunoregulatory factors were differentially affected by IFN-β1a. Conclusion: our study demonstrates that weekly i.m. injection of 30 μg of IFN-β1a induces the expression of soluble mediators that may suppress the activities of pro-inflammatory cytokines such as IL-1 and TNF-α.