Autoimmune kidney disease in MRL/lpr mice inhibited by OK-432; II. Effect of indomethacin.
We have reported that OK-432 (a streptococcal preparation) prevents the development of autoimmune kidney disease in MRL/Mp-lpr/lpr (MRL/lpr) mice and prolongs their survival time. In the present study, to clarify the mechanism of this action of OK-432, we examined whether the cyclooxygenase inhibitor indomethacin (IND) affects this inhibition by OK-432. It was reconfirmed that OK-432 prevented the development of autoimmune kidney disease and prolonged the survival time. This OK-432 effect was counteracted when IND was coadministered. Furthermore, OK-432 produced tumor necrosis factor (TNF)-alpha and prostaglandin (PG) E2 in the peritoneal fluids in this strain of mice. The coadministration of IND suppressed the PGE2 but not the TNF-alpha production. These results suggest the possibility that the inhibition of autoimmune kidney disease by OK-432 might be due to the induction of cyclooxygenase metabolites of arachidonic acid.
Mihara
M
M
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan.
Ohsugi
Y
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000097:blood; D001327:Autoimmune Diseases / Q000517:prevention & control*; D015232:Dinoprostone / Q000032:analysis; D004195:Disease Models, Animal; D007075:Immunoglobulin M / Q000097:blood; D007213:Indomethacin / Q000494:pharmacology*; D007674:Kidney Diseases / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010844:Picibanil / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D007075:Immunoglobulin M; D014409:Tumor Necrosis Factor-alpha; D010844:Picibanil; D015232:Dinoprostone; D007213:Indomethacin