Serum and liver concentrations of tumor necrosis factor α and interleukin-1β following administration of carbon tetrachloride to male rats

Inflammatory cytokines are recognized as early mediators of tissue damage and repair. The purpose of this study was to determine the effects of car-bon tetrachloride administration on tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) concentrations in serum and liver of rats. Administration of 0.2 ml/kg, i.p., of CCl4 to male Fischer 344 rats caused modest increases in serum levels of both cytokines; elevations of TNF-alpha were statistically significant at 4 and 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 affected. Treatment with 0.1, 0.32 or 1.0 ml/kg of CCl4 produced dose-dependent increases in serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities, but serum cytokine concentrations were not dose-dependent and did correspond with serum ALT and SDH activities. The results suggest that IL-1 beta production in rat liver is stimulated 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 organ other than liver. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.