Format

Send to

Choose Destination
Clin Exp Immunol. 1999 Jan;115(1):32-41.

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

Author information

1
Department of Rheumatology, Centre of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.

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.

PMID:
9933418
PMCID:
PMC1905187
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center