Abstract
COLLAGEN type II–induced arthritis (CIA) in DBA/1 mice is a well-established model for human rheumatoid arthritis and has been used extensively to elucidate pathogenic mechanisms as well as to identify potential targets for therapeutic intervention. The development of CIA is associated with high levels of cell-mediated and humoral immunity to collagen, and arthritis can be transferred both by antibodies against type II collagen (CII) and specific T cells. The role of B cells during the different phases of disease development is unclear. Some studies have demonstrated that anticollagen antibody levels do not correlate with disease severity in CIA. However, more recent reports have shown a crucial role for these cells, as well as anti-CII antibodies, in the development of CIA. The new immunosuppressive agent, LF 15-0195, obtained by organic synthesis, is an analog of 15-deoxyspergualin. This compound was designed to increase stability in water solution and resistance to in vivo oxidative metabolism. It is currently in human clinical development. The pharmacologic and mechanistic effects of LF 15-0195 in CIA were investigated in this study. We focused on short-term treatment (5 days) starting on the first day of clinical disease. The effect of LF 15-0195 treatment was monitored daily by clinical score and paw swelling during 30 days after the onset of clinical disease. The modification of humoral response to CII was determined by measurement of serum levels of anti-CII immunoglobulin isotypes produced during the course of arthritis.
Published Version
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