CGP 47969A: effect on collagen induced arthritis in DBA/1 mice.
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).


CONCLUSIONS
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.
Geiger
T
T
Department of Inflammation/Bone/Allergy, Ciba Geigy Ltd., CH-Basel, Switzerland.
Rordorf
C
C
Cosenti-Vargas
A
A
Ferrini
P G
PG
Widler
L
L
Glatt
M
M
Vosbeck
K
K
D000208:Acute Disease; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010879:Piperazines / Q000627:therapeutic use*; D011239:Prednisolone / Q000627:therapeutic use; D011859:Radiography; D000683:Serum Amyloid P-Component / Q000032:analysis
C092257:CGP 47969A; D007074:Immunoglobulin G; D010879:Piperazines; D000683:Serum Amyloid P-Component; D003094:Collagen; D011239:Prednisolone