Interferon beta-1b decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9

Ann Neurol. 1996 Dec;40(6):853-63. doi: 10.1002/ana.410400607.


In multiple sclerosis (MS), the influx of activated T lymphocytes into the brain parenchyma leads to the subsequent damage of oligodendrocytes, the cells that produce central nervous system (CNS) myelin. We report here that interferon beta-1b (IFNbeta-1b), a drug shown to be efficacious in the treatment of patients with MS, decreases the in vitro migration of activated T lymphocytes through fibronectin (FN), a major component of the basement membrane that surrounds cerebral endothelium. At 1,000 IU/ml, IFNbeta-1b reduced the migratory rate to that of unactivated T cells. In contrast, IFNgamma at 1,000 IU/ml, which caused a similar decrease (25%) in the proliferation rate of T lymphocytes as IFNbeta-1b, did not affect migration. All T-lymphocyte subsets and natural killer (NK) cells were demonstrated by flow cytometry to be equally affected by IFNbeta-1b treatment. 125I-Western blot analyses revealed that IFNbeta-1b treatment resulted in a marked reduction of the ability of T cells to cleave FN. The substrate-degrading capability of T lymphocytes was shown to be due predominantly to the activity of a 92-kd matrix metalloproteinase, MMP-9, whose levels were decreased by IFNbeta-1b. We suggest that the clinical benefits of IFNbeta-1b treatment in MS patients may be in part a result of the ability of this drug to significantly decrease MMP-9 activity, leading to a reduction of T-lymphocyte infiltration into the CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Cell Movement / drug effects*
  • Collagenases / metabolism*
  • Humans
  • Interferon beta-1a
  • Interferon beta-1b
  • Interferon-beta / pharmacology*
  • Killer Cells, Natural / cytology
  • Matrix Metalloproteinase 9
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / enzymology


  • Adjuvants, Immunologic
  • Interferon beta-1b
  • Interferon-beta
  • Collagenases
  • Matrix Metalloproteinase 9
  • Interferon beta-1a