EFFECT OF DIFFERENT SEPSIS-RELATED CYTOKINES ON LIPID-SYNTHESIS BY ISOLATED HEPATOCYTES

Cytokines seem to play an important role in the metabolic disturbances that are commonly associated with sepsis. In this study, we analyzed the effect of tumor necrosis factor, interleukin-l and interleukin-6, as well as that of tumor necrosis factor in combination with interleuk in-l or interleukin-6, both on free fatty acids and on phospholipid sy nthesis by isolated rat hepatocytes. Ah three cytokines and combinatio ns caused inhibited D [U-C-14]glucose incorporation into phosphatidylc holine (tumor necrosis factor = 6.39 +/- 1.13 pmol/mu g protein vs. co ntrol = 12.90 +/- 0.98 pmol/mu g protein, n = 7; p < 0.001). However, when [U-C-14]palmitate was used as radioactive precursor, tumor necros is factor, either alone or in the presence of the other cytokines, sti mulated phosphatidylcholine synthesis. D-[U-C-14]glucose incorporation into free fatty acids and triacylglycerol was also significantly stim ulated, whereas phosphatidylinositol labeling was found inhibited by t he assayed cytokines. Our results demonstrate an effect of sepsis-rela ted cytokines, more evident for tumor necrosis factor, on hepatocyte l ipid synthesis either from glucose or palmitate. Also, the findings su pport the hypothesis that cytokine-induced changes in hepatocyte lipid synthesis can contribute to the impairment in lipidic metabolism seen in patients with sepsis.