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

J. S. Alexander, M. K. Harris, S. R. Wells, G. Mills, K. Chalamidas, V. C. Ganta, J. McGee, M. H. Jennings, E. Gonzalez-Toledo, A. Minagar

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Background: Interferon-β1b (IFN-β1b), 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-β1b decreased serum MMP-8 and MMP-9 (not TIMP-1). Results: The sustained treatment with IFN-β1b 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-β1b 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-β1b during the first year of treatment.

Original languageEnglish (US)
Pages (from-to)801-809
Number of pages9
JournalMultiple Sclerosis
Volume16
Issue number7
DOIs
StatePublished - Jul 2010
Externally publishedYes

Keywords

  • IL-12
  • IL-17
  • IL-23
  • interferon-β1b
  • MMP-8
  • MMP-9
  • multiple sclerosis
  • TIMP-1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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