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IFN-beta1a may increase serum levels of TIMP-1 in patients with relapsing-remitting multiple sclerosis

E Waubant1, L Gee, K Miller

  • 1UCSF/Mt. Zion Multiple Sclerosis Center, San Francisco, CA 94115, USA. emmanuelle.waubant@psl.ap-hop-paris.fr

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
|May 2, 2001
PubMed

Insights

Interferon beta-1a treatment for multiple sclerosis (MS) did not alter matrix metalloproteinase-9 (MMP-9) levels. However, this therapy may increase levels of tissue inhibitor of MMP-1 (TIMP-1) in MS patients.

Area of Science:

  • Neuroimmunology
  • Biochemistry
  • Pharmacology

Background:

  • Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
  • Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a role in extracellular matrix remodeling and inflammation in MS.
  • Interferon-beta1a (IFN-beta1a) is a common disease-modifying therapy for relapsing-remitting MS.

Purpose of the Study:

  • To investigate the effect of IFN-beta1a treatment on serum levels of MMP-9 and TIMP-1 in patients with relapsing-remitting MS.
  • To determine if changes in MMP-9 or TIMP-1 correlate with therapeutic response.

Main Methods:

  • Serum samples were collected monthly from 7 relapsing-remitting MS patients for 6 months before and 6 months during weekly intramuscular IFN-beta1a (30 microg) treatment.
  • Serum concentrations of MMP-9 and TIMP-1 were quantified using appropriate assays.
  • Within-patient changes in MMP-9 and TIMP-1 levels were analyzed using the Wilcoxon signed-rank test.

Main Results:

  • Serum MMP-9 levels remained unchanged during IFN-beta1a treatment compared to pretreatment levels.
  • Serum TIMP-1 levels were significantly higher during the first 6 months (p = 0.10) and specifically during months 4-6 (p = 0.047) of IFN-beta1a treatment compared to pretreatment levels.
  • The median TIMP-1 level increased from 414 ng/ml pretreatment to 771.5 ng/ml during months 1-6 and 793 ng/ml during months 4-6 of treatment.

Conclusions:

  • IFN-beta1a therapy in relapsing-remitting MS patients does not appear to alter serum MMP-9 levels.
  • Preliminary findings suggest that IFN-beta1a treatment may lead to an increase in serum TIMP-1 levels.
  • Further research is warranted to elucidate the role of TIMP-1 modulation by IFN-beta1a in MS pathogenesis and treatment response.

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