Alterations in serum MMP-8, MMP-9, IL-12p40 and IL-23 in multiple sclerosis patients treated with interferon-beta 1b

作者：Alexander J S; Harris M K; Wells S R; Mills G; Chalamidas K; Ganta V C; McGee J; Jennings M H; Gonzalez Toledo E; Minagar A^*

来源：Multiple Sclerosis, 2010, 16(7): 801-809.

DOI：10.1177/1352458510370791

• IL-12
• IL-23
• IL-17
• interferon-beta 1b
• MMP-8
• MMP-9
• multiple sclerosis
• TIMP-1

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.

• 出版日期2010-7