Mechanism of interleukin-6 induction by intraperitoneal administration of carbon tetrachloride and its effect on hepatic injury

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Carbon tetrachloride has been used as a model compound for studying hepatotoxicity. We previously demonstrated that a high level of interleukin (IL)-6 was induced in the early period after carbon tetrachloride administration via the intraperitoneal or subcutaneous mute, but not via the oral mute, in rats and it was produced at least partially by peritoneal cells in the serous membrane of the peritoneum through various inflammatory factors. In the present study we examined the mechanisms of IL-6 production and up-regulation of protective proteins by endogenously induced IL-6. Levels of inflammatory factors such as IL-la, IL-1B, tumor necrosis factor-a and pmstaglandin E_2 were increased and number of peritoneal cells was decreased in the peritoneum immediately after intraperitoneal carbon tetrachloride administration, and both increase in inflammatory factors and lass of cells were reduced as the vehicle-to-carbon tetrachloride was increased. It was considered that carbon tetrachloride … More dissolved in a small dose of vehicle easily reacted with membrane lipid components and caused activation or lysis of peritoneal cells to release inflammatory factors. IL-1a seems to contribute to IL-6 production most effectively among the inflammatory factors, judging from its high IL-6-inducing potency and concentration in the peritoneal exudate. Heme oxygenase-1 (HO-1) was induced more in rats administered carbon tetrachloride intraperitoneally compared with orally ; while, expression of heat shock protein (HSP) 72 and HSP90 were increased to similar extents in both experimental groups. The fact that the HO-1 expression was partially reduced by pretreatment with anti-rat IL-6 antibody shows that hepatic HO-1. is up-regulated by endogenously induced by .IL-6, in addition to its up-regulation by heme derived from cytochrome P450 which has already been reported. Since HO-1 is known to reduce tissue injuries, the present findings should be taken into consideration during the analysis of data using the carbon tetrachloride-induced liver injury model. Less