The effect of SM-8849 on experimental arthritis in mice.
The effect of a novel thiazole derivative, SM-8849, on experimental arthritis in mice was studied and compared to that of prednisolone. SM-8849 and prednisolone reduced the incidence and severity of type II collagen-induced arthritis in mice, as assayed by clinical observation and histopathological studies. Although both agents inhibited type II collagen-induced delayed type hypersensitivity (DTH) in arthritic mice, SM-8849 did not affect the production of humoral antibodies to type II collagen. To examine the inhibitory mechanism of SM-8849, the effects on T cell-dependent allergic inflammation were studied. SM-8849 clearly inhibited T cell-dependent reactions including staphylococcal enterotoxin B (SEB)-induced arthritis, SEB-induced CD25 expression on T cells and sheep red blood cell (SRBC)-induced DTH reaction. SM-8849, however, had no effect on the production of humoral antibody forming cells in the spleen of mice immunized with SRBC. These results indicate that inhibition of type II collagen-induced arthritis by SM-8849 is mainly due to the inactivation of T cells that are related to DTH reaction.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Takaoka
Y
Y
Kuwabara
K
K
Kamada
H
H
Kitagaki
K
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D000921:Antibody-Producing Cells / Q000276:immunology; D001168:Arthritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology; D002417:Cattle; D003094:Collagen / Q000276:immunology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000276:immunology; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D007114:Immunization; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011239:Prednisolone / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013844:Thiazoles / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D001713:Biphenyl Compounds; D015704:CD4 Antigens; D004768:Enterotoxins; D015375:Receptors, Interleukin-2; D018089:Superantigens; D013844:Thiazoles; C072865:4-(1-(2-fluoro-4-biphenyl)ethyl)-2-methylaminothiazole; C031818:enterotoxin B, staphylococcal; D003094:Collagen; D011239:Prednisolone