期刊
MULTIPLE SCLEROSIS JOURNAL
卷 16, 期 7, 页码 801-809出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458510370791
关键词
IL-12; IL-23; IL-17; interferon-beta 1b; MMP-8; MMP-9; multiple sclerosis; TIMP-1
资金
- Bayer Healthcare Pharmaceuticals
Background: Interferon-beta 1b (IFN-beta 1b), an effective treatment for multiple sclerosis (MS), lessens disease severity in MS patients. However, the mechanisms of its immunoregulatory and anti-inflammatory effects in MS remain only partially understood. Matrix metalloproteinases (MMP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are involved in blood brain barrier disruption and formation of MS lesions. Th1/Th17 cytokines e.g. interleukins IL-12p40, IL-17, and IL-23, are associated with MS disease activity and are significant players in pathogenesis of MS. Objective: During a 1-year prospective study, we serially measured serum MMP-8, MMP-9, TIMP-1, IL-12p40, IL-17, and IL-23 in 24 patients with relapsing-remitting MS. We compared the results to clinical course and to brain magnetic resonance imaging. IFN-beta 1b decreased serum MMP-8 and MMP-9 (not TIMP-1). Results: The sustained treatment with IFN-beta 1b attenuated the pro-inflammatory environment by significantly reducing the serum IL-12p40, IL-23, and showed a trend for decreasing IL-17. Decreased serum MMP-8, MMP-9, IL-12 and IL-23 levels were correlated with a decrease in the number of contrast-enhanced T2-weighted lesions. Conclusion: Early treatment of MS with IFN-beta 1b may stabilize clinical disease by attenuating levels of inflammatory cytokines and MMPs. Serial measurement of inflammatory mediators may serve as sensitive markers to gauge therapeutic responses to IFN-beta 1b during the first year of treatment.
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