Effect of nitric oxide synthase inhibition on Schistosoma japonicum egg-induced granuloma formation in the mouse liver

Nitric oxide (NO) plays diverse roles in a variety of pathological processe s. We investigated the role of NO in Schistosoma japonicum egg-induced gran uloma formation in a mouse hepatic model. Immunohistological analysis revea led that there is the most intense and extensive inducible nitric oxide (iN OS) expression 2 weeks after egg implantation, and thereafter it decreased considerably with time. Treatment with nitric oxide synthase inhibitors, NI L (L-N-6- (iminoethyl)-lysine) or N omega -nitro-L-arginine methyl ester (L -NAME), resulted in two different types of unusual granulomas at 2 weeks. O ne type showed suppressed fibrosis; while another showed foreign body-type multinuclear cell formation which frequently appeared particularly when 50 mug/ml NIL was given. At 3 weeks following treatment, fibrotic granulomas w ith scanty peripheral cellularity was obvious. However there were no appare nt changes after this period (at 4 weeks). Cytokine analysis in NIL-treated mice showed a significant increase of IL-4 and IL-13 production at 2 weeks . These findings indicated that nitric oxide contributes to granuloma devel opment during the early stages probably through the regulation of Th2 cytok ine production.