CNI-1493, an inhibitor of proinflammatory cytokines, retards cartilage destruction in rats with collagen induced arthritis

Abstract

Objective: To investigate if administration of CNI-1493, an inhibitor of the synthesis of proinflammatory cytokines and NO, protects against development of joint destruction in collagen induced arthritis (CIA) in rats.

Methods: In a placebo controlled experiment, CNI-1493 was given once daily intraperitoneally after onset of clinical arthritis in DA rats. Disease progression was studied by clinical scoring of arthritis, serial measurement of serum levels of COMP, and histological examination of joints.

Results: Clinical signs of arthritis were significantly reduced in the CNI-1493 treated group of rats in comparison with the placebo treated group. Histological examinations of paws demonstrated a significant reduction of cartilage destruction in the CNI-1493 treated group, but marked destruction of cartilage in the placebo group. Serum levels of COMP increased in the placebo group, whereas in the CNI-1493 treated group levels were low and decreased significantly during the observation time.

Conclusions: Treatment with CNI-1493 provides efficient protection against synovial inflammation and cartilage destruction when used therapeutically in CIA. The protective effect against cartilage destruction can be monitored by measuring serum COMP. These observations make CNI-1493 an attractive candidate for therapeutic studies in human arthritis, and COMP an attractive serum marker for monitoring joint protective effects.

Figure 1

Disease scores. The maximum score in the arthritic model is 16 points. From day 19 the placebo group has a significantly higher score than the CNI-1493 treated group (except at day 23). CNI-1493 at days 14–22, n = 13; at days 22–23, n = 12; at days 24–26, n = 7. Placebo at days 14–23, n = 14; at days 24–26, n = 9. All values are medians (interquartile range). *p<0.05 CNI group v placebo group.

Figure 2

Serum levels of COMP. CNI-1493 at day 14, n = 13; at day 23, n = 5; and at day 26, n = 7. Placebo at day 14, n = 14; at day 23, n = 5; and at day 26, n = 9. All values are medians (interquartile range). *p<0.05 CNI group v placebo group.