Interferon beta-1b inhibits gelatinase secretion and in vitro migration of human T cells: a possible mechanism for treatment efficacy in multiple sclerosis

Ann Neurol. 1996 Dec;40(6):846-52. doi: 10.1002/ana.410400606.


Treatment with interferon beta-1b has substantial clinical benefit in the demyelinating disease multiple sclerosis, yet the mechanism of action in the disease remains largely unknown. Gelatinase A (matrix metalloproteinase-2, 72-kd gelatinase) and B (matrix metalloproteinase-9, 92-kd gelatinase) are matrix metalloproteinases capable of enzymatic digestion of subendothelial basement membrane constituents. In human T cells, interleukin-2 induces gelatinase secretion and enhances gelatinase-dependent migration across an artificial basement membrane-like layer in vitro. Pretreatment of T cells with interferon beta-1b for 48 hours decreased interleukin-2-induced gelatinase production and secretion as determined by zymography. In parallel to the downregulation of gelatinase secretion, pretreatment with interferon beta-1b inhibited T-cell migration across the basement membrane in vitro by up to 90%, but had only a minor impact on cell locomotion per se. For both gelatinase secretion and T-cell migration, the inhibitory effect mediated by exposure to interferon beta-1b was dose dependent. Fluorescence-activated cell sorter analysis also showed that interferon beta-1b downregulates the interleukin-2 receptor alpha-chain and lowered the affinity of interleukin-2 to the cell surface by 30%, which may represent an additional mechanism for the observed effects of interferon beta-1b. The dramatic effects of interferon beta-1b on gelatinase expression and migration raise the possibility that its beneficial effects in multiple sclerosis may result from interference with the capacity of activated T cells to traverse the basement membrane and migrate to the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use*
  • Cell Movement / drug effects
  • Collagenases / metabolism*
  • Gelatinases / metabolism*
  • Humans
  • Interferon beta-1a
  • Interferon beta-1b
  • Interferon-beta / pharmacology
  • Interferon-beta / therapeutic use*
  • Interleukin-2 / pharmacology
  • Interleukin-2 / therapeutic use
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / metabolism*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / enzymology*
  • Multiple Sclerosis / immunology
  • T-Lymphocytes / cytology*


  • Adjuvants, Immunologic
  • Interleukin-2
  • Interferon beta-1b
  • Interferon-beta
  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Interferon beta-1a