The dynamics of induced histamine and its protective effect on hepatitis in Propionibacterium acnes-primed lipopolysaccharide-induced acute liver injury in mice

P. acnes-primed and LPS-induced hepatitis in mice has been demonstrated to be mediated by the production of IL- 18. In the previous study, we found that histamine(HA) inhibited IL-18 initiated cytokine production. In the present study, we examined the dynamics of endogenous HA in the liver of this model and investigated the involvement of HA in the occurrence of hepatitis, especially focused on the regulation of cytokine production. We also analyzed the significance of HA in the development of hepatitis using HDC-KO mice. We observed a transient increase in HDC activity associated with the elevation of HA and t-MH levels in the liver of wild-type mice at 6h after the injection of LPS. The plasma AST and ALT levels in HDC-KO mice were much higher than those in the wild-type mice. The pretreatment of wild- type mice with famotidine aggravated hepatitis and induced higher levels of plasma cytokine responses whereas d-chlorpheniramine did not. Also, the liver injury as well as plasma cytokine levels in HDC-KO mice were much higher than those in wild-type mice. These results suggested that endogenously produced HA exerts a protective role for the development of hepatitis in this model.