Autoimmune kidney disease in MRL/lpr mice inhibited by OK-432; II. Effect of indomethacin.

Abstract

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.