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Anti-inflammatory effects of a new tumour necrosis factor-alpha (TNF-alpha) inhibitor (CNI-1493) in collagen-induced arthritis (CIA) in rats.

Authors
  • kerlund, K
  • Erlandsson Harris, H
  • Tracey, K J
  • Wang, H
  • Fehniger, T
  • Klareskog, L
  • Andersson, J
  • Andersson, U
Type
Published Article
Journal
Clinical and experimental immunology
Publication Date
Jan 01, 1999
Volume
115
Issue
1
Pages
32–41
Identifiers
PMID: 9933418
Source
Medline
License
Unknown

Abstract

A recently developed compound, a multivalent guanylhydrazone (CNI-1493) that inhibits TNF-alpha production by suppressing TNF-alpha translational efficiency, was administered in an experimental model of collagen type II-induced arthritis in DA rats. CNI-1493 was injected daily intraperitoneally either before the onset of arthritis or after the establishment of clinical disease. Prophylactic treatment with CNI-1493 significantly prevented or delayed the onset and suppressed the severity of arthritis in a dose-dependent manner. Therapeutic intervention with CNI-1493 in established joint disease also resulted in a significant reduction of clinical signs of arthritis in treated animals. No severe side-effects were noted when animals were treated with daily CNI-1493 doses up to 5 mg/kg. An immunohistochemical study was performed which demonstrated that CNI-1493 led to a reduced expression of TNF-alpha at the site of disease activity. Thus, CNI-1493 with documented inhibitory effects on TNF-alpha synthesis, has proven successful in ameliorating the course of arthritis in CIA. We believe that the use of a compound such as CNI-1493 with a defined mode of action provides a useful tool for dissecting and understanding important pathogenic mechanisms operating in the development of chronic arthritis.

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