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 4h. TNF-alpha and IL-1beta levels gradually increased, reaching the maximum at 24h. IL-10 level transiently peaked at 4h and then decreased, but later further increased, reaching the second peak at 24h. Plasma alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities peaked at 24h. 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.
Zuinen
Ryoji
R
Department of Hygienic Chemistry, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-8543, Japan.
Yamaji
Kenzaburo
K
Aoki
Miho
M
Chikuma
Toshiyuki
T
Hojo
Hiroshi
H
D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000276:immunology*; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D010529:Peritoneal Cavity; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D015850:Interleukin-6; D002251:Carbon Tetrachloride