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CGP 47969A: effect on collagen induced arthritis in DBA/1 mice
T Geiger1, C Rordorf, A Cosenti-Vargas
1Department of Inflammation/Bone/Allergy, Ciba Geigy Ltd., CH-Basel, Switzerland.
Objective:
CGP 47969A is a novel and potent inhibitor of cytokine biosynthesis in human and murine monocytic cells. The effect of CGP 47969A on collagen induced arthritis (CIA) in DBA/1 mice was investigated and compared to that of prednisolone.
Methods:
CIA was induced by intradermal injection of type II collagen in CFA at Day 0. CGP 47969A was applied orally, 5 times/week, starting at Day 15 after immunization. Arthritic signs were recorded 3 times/week for clinical scoring and radiographic analysis was performed at the end of the experiment at Day 60. Serum amyloid P (SAP) and anticollagen antibody titers were determined 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 arthritis (ED50 between 1 and 5 mg/kg). Prednisolone at 3 and 30 mg/kg reduced the arthritis incidence to 70 and 30%, respectively. CGP 47969A dose dependently inhibited the joint destruction, as measured by radiographic scoring and its potency was comparable to that of prednisolone. The elevated serum levels of the positive acute phase protein SAP in arthritic animals were completely normalized by CGP 47969A at a dose of 60 mg/kg, however, neither CGP 47969A nor prednisolone influenced 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 justify the expectation that this novel antiarthritic compound now under development might also be effective in the treatment of rheumatoid arthritis in man.
Insights
CGP 47969A effectively treats collagen-induced arthritis (CIA) in mice by reducing joint inflammation and destruction. This novel compound shows potency comparable to prednisolone, suggesting potential for human rheumatoid arthritis treatment.
Area of Science:
- Immunology
- Pharmacology
- Rheumatology
Background:
- Cytokine biosynthesis inhibitors are crucial for managing inflammatory conditions.
- Collagen-induced arthritis (CIA) in DBA/1 mice serves as a model for human rheumatoid arthritis.
Purpose of the Study:
- To evaluate the efficacy of CGP 47969A, a novel cytokine biosynthesis inhibitor, in a mouse model of arthritis.
- To compare the anti-arthritic effects of CGP 47969A with prednisolone.
Main Methods:
- Collagen-induced arthritis (CIA) was induced in DBA/1 mice.
- CGP 47969A was administered orally, and arthritic signs were monitored.
- Radiographic analysis, serum amyloid P (SAP) levels, and anticollagen antibody titers were assessed.
Main Results:
- CGP 47969A dose-dependently reduced arthritis incidence, with significant prevention at higher doses.
- The compound inhibited joint destruction, showing potency comparable to prednisolone.
- CGP 47969A normalized elevated serum SAP levels in arthritic mice.
Conclusions:
- CGP 47969A demonstrates significant efficacy in collagen-induced arthritis.
- Its potency is comparable to prednisolone, supporting its potential as an anti-rheumatic drug.
- Further investigation into CGP 47969A for treating human rheumatoid arthritis is warranted.