CGP 47969A - EFFECT ON COLLAGEN-INDUCED ARTHRITIS IN DBA 1 MICE/

Objective. CGP 47969A is a novel and potent inhibitor of cytokine bios ynthesis in human and murine monocytic cells. The effect of CGP 47969A on collagen induced arthritis (CIA) in DBA/1 mice was investigated an d compared to that of prednisolone. Methods. CIA was induced by intrad ermal injection of type II collagen in CFA at Day 0. CGP 47969A was ap plied orally, 5 times/week, starting at Day 15 after immunization. Art hritic signs were recorded 3 times/week for clinical scoring and radio graphic analysis was performed at the end of the experiment at Day 60. Serum amyloid P (SAP) and anticollagen antibody titers were determine d by ELISA at Day 60. Results. CGP 47969A dose dependently reduced the incidence of arthritis from 93% in the positive control group to 60, 40, 30 and 10% at doses of 1, 5, 25 and 60 mg/kg/day, respectively. At a dose of 120 mg/kg, CGP 47969A totally prevented the occurrence of a rthritis (ED(50) between 1 and 5 mg/kg). Prednisolone at 3 and 30 mg/k g reduced the arthritis incidence to 70 and 30%, respectively. CGP 479 69A dose dependently inhibited the joint destruction, as measured by r adiographic scoring and its potency was comparable to that of predniso lone. The elevated serum levels of the positive acute phase protein SA P in arthritic animals were completely normalized by CGP 47969A at a d ose of 60 mg/kg, however, neither CGP 47969A nor prednisolone influenc ed the plasma levels of anticollagen antibodies (IgG). Conclusion. Our results demonstrate that CGP 47969A is highly effective in CIA with a potency comparable to that of prednisolone. These promising results j ustify the expectation that this novel antiarthritic compound now unde r development might also be effective in the treatment of rheumatoid a rthritis in man.