Migratory behavior of lymphocytes isolated from multiple sclerosis patients: Effects of interferon β-1b therapy

Joon H. Uhm, Nora P. Dooley, Olaf Stuve, Gordon S. Francis, Pierre Duquette, Jack P. Antel, Voon Wee Yong

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Previous reports by our group and by others have shown that in vitro treatment of T cells derived from healthy, normal subjects with interferon β-1b (IFN-β1b) reduces metalloproteinase (metalloproteinase type 9 [MMP-9]) activity with a consequent reduction in lymphocyte migration. In this study, we used a Boyden chamber assay to assess the migratory capacity of T cells derived from multiple sclerosis patients who either did or did not receive IFN-β1b. Lymphocytes derived from patients treated for less than 2 years with IFN-β migrated at a low rate that was indistinguishable from that of cells isolated from healthy donors. However, longer term treatment with IFN (>3.5 years) was associated with a reversion of the migration to a high level that did not differ statistically from that of cells isolated from untreated multiple sclerosis patients. For both high-migratory groups, migration could be reduced to control levels after the exogenous addition of TIMP-1, a relatively specific inhibitor of the MMP-9, implicating this protease in the process of T-cell migration. Our findings suggest that one of the mechanisms by which IFN-β exerts its action is by reducing MMP-9 activity and thus the entry of inflammatory cells into the nervous system and, as such, MMPs may constitute potential therapeutic targets in inflammatory diseases such as multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)319-324
Number of pages6
JournalAnnals of neurology
Volume46
Issue number3
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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