Interferon beta-1b treatment does not induce autoantibodies

Background: There is little information regarding the potential of interferon beta ( IFN beta) to induce or exacerbate autoimmune disease. Existing data from uncontrolled studies are contradictory and do not differentiate between autoimmune dysfunction, which is frequent in patients with multiple sclerosis ( MS), and untoward drug effects. Objective: To evaluate the impact of IFN beta on hepatic, thyroid, and other markers of autoimmunity using data from the European placebo-controlled double-blind, multicenter study of IFN beta-1b in patients with secondary progressive MS ( SPMS). Methods: Serum samples obtained at baseline and at 6- month intervals for 24 months were analyzed for the following autoantibodies ( AAbs): antinuclear ( ANA), antimitochondrial ( AMA), smooth muscle ( SMA), liver kidney microsome ( LKM), thyroid microsome ( TPO), and human thyroglobulin ( TG). AAb status at baseline and during treatment was related to respective laboratory and clinical deviations. Results: The analysis of AAb data included 355 patients receiving IFN beta-1b and 353 receiving placebo. There was no difference between treatment groups in de novo AAb positivity. A greater proportion of women were AAb positive at baseline and during treatment. No association was found between liver enzyme elevations and ANA, AMA, or SMA antibody formation in either treatment group. Laboratory- based thyroid alterations during the study were significantly related to TG/TPO status at baseline but were not associated with IFN beta-1b treatment. Adverse events possibly indicative of other diseases with autoimmune links were not associated with respective AAb status. Conclusion: Interferon beta- 1b treatment did not induce autoantibody formation in this population of patients with secondary progressive multiple sclerosis

Monocyte-derived cytokines in multiple sclerosis

MS is an inflammatory, presumably autoimmune, disease mediated by the activation of T cells, B cells and monocytes (MO). Inflammation is thought to occur early during the relapsing-remitting phase of MS (RRMS), whereas in the later phases of MS such as secondary progressive MS (SPMS), inflammation tends to diminish. Our objective was to compare the types and amounts of proinflammatory and regulatory cytokines produced by MO from relapsing–remitting patients with or without treatment with IFN-β (RRMS(+) therapy, RRMS(−) therapy), respectively, from secondary progressive patients (SPMS) and from healthy controls (HC). MO were isolated by a density-gradient technique and three different techniques (RNase protection assay, ELISA and intracellular cytokine staining) were used to assess cytokine levels. An increase in IL6, IL12 and TNF-α was observed by all three methods for RRMS(−) therapy and for SPMS patients compared to HC and RRMS(+) therapy patients. We conclude that proinflammatory and regulatory monokines can be derived from MO of MS patients and that these levels are modulated by IFN-β therapy. Although it is believed that inflammation tends to diminish in SPMS patients, our data show that inflammatory cytokines continue to be released at high levels, suggesting that IFN-β or IL10 treatment may be beneficial for this group