Early induced, high-level interleukin-6 expression in the rat peritoneal cavity into which a hepatotoxicant carbon tetrachloride was administered

IL-6 induction depending on the mode of carbon tetrachloride (CCl4) administration was investigated in rats. After the intraperitoneal (i.p.) administration of CCl4 in 50% corn oil at 1.0 ml/kg body weight, IL-6 level markedly increased in plasma and peaked at 4 h. TNF-α and IL-1β levels gradually increased, reaching the maximum at 24 h. IL-10 level transiently peaked at 4 h and then decreased, but later further increased, reaching the second peak at 24 h. Plasma alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities peaked at 24 h. As the vehicle-to-CCl4 ratio increased, the level of IL-6 decreased and the activities of ALT and SDH increased. After oral CCl4 administration, IL-6 was not significantly detected. IL-6 level in peritoneal exudate fluid (PEF) increased simultaneously with plasma IL-6 level after i.p. CCl4 administration, but the total amount of PEF IL-6 was 37-fold as much as that of plasma IL-6, in contrast to the result that the total amount of plasma IL-6 was 19-fold as much as that of PEF IL-6 after i.p. lipopolysaccharide administration. These results suggest that i.p. administration of CCl4 dissolved in a small amount of vehicle selectively induces a high production of IL-6 in the peritoneal cavity early after the administration. Since IL-6 is a protective cytokine against hepatotoxicity, its induction should be taken into consideration during analysis of data obtained using the CCl4-induced liver injury model.