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-beta 1a

Background: interferon beta (IFN-beta) reduces relapse rate and disease pro gression in patients with the relapsing-remitting form of multiple sclerosi s (RRMS), IFN-beta may act by upregulating the expression of anti-inflammat ory components of the immune system. Objectives: To determine whether weekl y intramuscular (i.m.) injection of IFN-beta 1a had a short- or long-term e ffect 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-alpha RI and sTNF-a lpha RII), and soluble E-selectin (sE-Sel) were followed over time in ten p atients with RRMS who were treated with weekly i.m. injections of 30 mu g ( = 6 MU) of IFN-beta 1a, Patient sera were sampled before, and 24, 48, 72, 9 6, and 168 hours after the first IFN-beta 1a injection (short-term), and th en at 1, 3, 6, 9 and 12 months after therapy initiation (long-term); highly sensitive, commercially available ELISA tests were used. Results: serum le vels of IL-1Ra, sTNF-alpha RI and sTNF-alpha RII, but not sE-Sel were signi ficantly increased in both short- and long-term follow-up. Interestingly, I L-1Ra, sTNF-alpha RI and sTNF-alpha RII behaviors were completely different , suggesting that these naturally occurring immunoregulatory factors were d ifferentially affected by IFN-beta 1a. Conclusion: our study demonstrates t hat weekly i.m. injection of 30 mu g of IFN-beta 1a induces the expression of soluble mediators that may suppress the activities of pro-inflammatory c ytokines such as IL-1 and TNF-alpha.