Matrix metalloproteinase upregulation in chronic inflammatory demyelinating polyneuropathy and nonsystemic vasculitic neuropathy

Neurology. 1999 Jul 13;53(1):62-70. doi: 10.1212/wnl.53.1.62.


Objective: To determine the expression pattern and cellular source of matrix metalloproteinases (MMPs) in chronic inflammatory demyelinating polyneuropathy (CIDP) and nonsystemic vasculitic neuropathy (NSVN).

Background: MMPs are endopeptidases involved in tissue destruction and infiltration by immune cells in multiple sclerosis and Guillain-Barré syndrome. Enzyme inhibitors of MMPs attenuate clinical symptoms in corresponding animal models of these diseases. MMP inhibition may therefore be a novel approach for the treatment of CIDP and NSVN. However, the spectrum of MMPs expressed in chronic inflammatory neuropathies has not been established.

Methods: The expression of MMP-2, MMP-3, MMP-7, and MMP-9 in T cells, macrophages, and stromal cells in CIDP, NSVN, and noninflammatory neuropathies (NIN) was quantitated by immunohistochemistry. Results were correlated with clinical and electrophysiologic findings.

Results: The production of MMP-2 and MMP-9 is increased in nerve tissue in CIDP and NSVN compared with NIN. T cells are the predominant source of MMP-2 and MMP-9 in CIDP and NSVN, whereas macrophages contribute only to a minor extent. Stromal cells of the perineurium/epineurium are an additional source of MMP-2 in NSVN, but not in CIDP. Expression of MMP-3 and MMP-7 was not detectable in CIDP or NSVN. Expression of MMP-2 and MMP-9 did not correlate with clinical disease activity and electrophysiologic measurements.

Conclusions: The upregulation of MMP-2 and MMP-9 is a specific feature of CIDP and NSVN, and selective inhibitors of these enzymes could be used to prevent inflammatory tissue damage. The similar increase of MMP-2 and MMP-9 in both demyelinating (CIDP) and nondemyelinating (NSVN) neuropathies raises doubts about whether MMPs play a primary role in demyelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chronic Disease
  • Collagenases / metabolism
  • Demyelinating Diseases / enzymology*
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / physiopathology
  • Female
  • Gelatinases / metabolism
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Inflammation
  • Macrophages / enzymology
  • Male
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 7
  • Matrix Metalloproteinase 9
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / metabolism*
  • Middle Aged
  • Peripheral Nervous System Diseases / enzymology*
  • Peripheral Nervous System Diseases / pathology
  • Peripheral Nervous System Diseases / physiopathology
  • Polyradiculoneuropathy / enzymology*
  • Polyradiculoneuropathy / pathology
  • Polyradiculoneuropathy / physiopathology
  • Stromal Cells / enzymology
  • Sural Nerve / enzymology
  • Sural Nerve / pathology
  • T-Lymphocytes / enzymology
  • Vasculitis / enzymology*
  • Vasculitis / pathology
  • Vasculitis / physiopathology


  • Collagenases
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 7
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9