A combined inhibitor of matrix metalloproteinase activity and tumour necrosis factor-alpha processing attenuates experimental autoimmune neuritis

E. J. Redford, K. J. Smith*, N. A. Gregson, M. Davies, P. Hughes, A. J.H. Gearing, K. Miller, R. A.C. Hughes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Citations (SciVal)

Abstract

Matrix metalloproteinases (MMPs) and the cytokine tumour necrosis factor (TNF)-alpha are implicated in the pathology of inflammatory demyelinating diseases of the CNS, and may also be involved in peripheral demyelinating diseases such as acute inflammatory demyelinating polyradiculoneuropathy. We have tested an inhibitor of MMP activity and TNF-alpha processing, BB-1101, in experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré syndrome. Treatment with BB-1101 from the time of immunization prevented the development of EAN, and when given from the onset of symptoms, it significantly reduced disease severity. These results indicate that MMPs and/or TNF-alpha are involved in the pathogenesis of EAN, and that drugs of this type may have potential as novel therapeutic agents in the therapy of peripheral nervous system demyelinating diseases.

Original languageEnglish
Pages (from-to)1895-1905
Number of pages11
JournalBrain
Volume120
Issue number10
DOIs
Publication statusPublished - 01 Oct 1997
Externally publishedYes

Keywords

  • Demyelination
  • Experimental autoimmune neuritis
  • Inflammation
  • Matrix metalloproteinases
  • Tumour necrosis factor-α
  • Immunohistochemistry
  • Benzyl Compounds
  • Pentoxifylline/pharmacology
  • Rats, Inbred Lew
  • Extracellular Matrix/enzymology
  • Rats
  • Male
  • Protease Inhibitors/pharmacology
  • Neuritis, Autoimmune, Experimental/physiopathology
  • Tissue Distribution
  • Tumor Necrosis Factor-alpha/antagonists & inhibitors
  • Animals
  • Succinates
  • Sciatic Nerve/enzymology
  • Dexamethasone/pharmacology
  • Female
  • Drug Combinations
  • Gelatinases/metabolism
  • Metalloendopeptidases/antagonists & inhibitors

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