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

1999; Oxford University Press; Volume: 115; Issue: 1 Linguagem: Inglês

10.1046/j.1365-2249.1999.00750.x

1365-2249

Karin Åkerlund, Helena Erlandsson Harris, Kevin J. Tracey, Haichao Wang, Todd A. Fehniger, Lars Klareskog, Jan Andersson, Jan Andersson,

Cytokine Signaling Pathways and Interactions

SUMMARY A recently developed compound, a multivalent guanylhydrazone (CNI-1493) that inhibits TNF-α production by suppressing TNF-α 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-α at the site of disease activity. Thus, CNI-1493 with documented inhibitory effects on TNF-α 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.