Inhibition of collagen II-induced arthritis in mice--a comparison of the effects of Sch 24937, immunosuppressants and nonsteroidal antiinflammatory drugs on the clinical expression of disease.
Previous studies from this laboratory have described Sch 24937 as a potent immunosuppressive agent that is particularly effective in suppressing humoral immune responses in mice. These findings prompted an evaluation of the effects of Sch 24937 in type II collagen-induced arthritis in mice where disease manifestations include the development of a strong humoral response to the collagen antigen. Sch 24937 reduced the incidence and severity of arthritis in collagen sensitized mice which appeared to be directly related to the immunosuppressive properties of the drug. However in contrast to the steroid betamethasone which also exhibited immunosuppressive activity, Sch 24937 did not prevent the changes occurring in the lymphocyte population of the draining lymph nodes of mice immunized with type II collagen. While the exact mechanism of the immunosuppressive activity of Sch 24937 remains to be elucidated, its mode of action in suppressing arthritis differs at least to some extent from that of a steroid.
Smith
S R
SR
Department of Allergy and Inflammation, Schering-Plough Research, Bloomfield, New Jersey 07003.
Pennline
K J
KJ
Bober
L A
LA
Kenworthy-Bott
L
L
Phillips
L
L
Pellerito
F
F
da Fonseca
M
M
Terminelli
C
C
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001168:Arthritis / Q000139:chemically induced / Q000517:prevention & control*; D001169:Arthritis, Experimental / Q000517:prevention & control*; D001623:Betamethasone / Q000627:therapeutic use; D003094:Collagen / Q000276:immunology*; D007114:Immunization; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use; D008198:Lymph Nodes / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D010641:Phenotype; D011725:Pyridines / Q000627:therapeutic use*; D013154:Spleen / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D007211:Indoles; D011725:Pyridines; C054872:Sch 24937; D003094:Collagen; D001623:Betamethasone; D007213:Indomethacin