SERUM AND LIVER CONCENTRATIONS OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-BETA FOLLOWING ADMINISTRATION OF CARBON-TETRACHLORIDE TO MALE RATS

Inflammatory cytokines are recognized as early mediators of tissue dam age and repair. The purpose of this study was to determine the effects of car-bon tetrachloride administration on tumor necrosis factor-alph a (TNF-alpha) and interleukin 1 beta (IL-1 beta) concentrations in ser um and liver of rats. Administration of 0.2 ml/kg, i.p., of CCl4 to ma le Fischer 344 rats caused modest increases in serum levels of both cy tokines; elevations of TNF-alpha were statistically significant at 4 a nd 12 h, and elevations of IL-1 beta were statistically significant at 24 h. Although CCl4 produced substantial increases in liver IL-1 beta concentrations (more than 3-fold), levels of TNF-alpha were not affec ted. Treatment with 0.1, 0.32 or 1.0 ml/kg of CCl4 produced dose-depen dent increases in serum alanine aminotransferase (ALT) and sorbitol de hydrogenase (SDH) activities, but serum cytokine concentrations were n ot dose-dependent and did correspond with serum ALT and SDH activities . The results suggest that IL-1 beta production in rat liver is stimul ated by hepatotoxic doses of CCl4. Production of TNF-alpha may also be induced, but the source of TNF-alpha in serum could be a tissue or or gan other than liver. (C) 1998 Elsevier Science Ireland Ltd. All right s reserved.