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 interleukin-l or interleukin-6, both on free fatty acids and on phospholipid synthesis by isolated rat hepatocytes. Ah three cytokines and combinations caused inhibited D [U-C-14]glucose incorporation into phosphatidylcholine (tumor necrosis factor = 6.39 +/- 1.13 pmol/mu g protein vs. control = 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 necrosis factor, either alone or in the presence of the other cytokines, stimulated phosphatidylcholine synthesis. D-[U-C-14]glucose incorporation into free fatty acids and triacylglycerol was also significantly stimulated, whereas phosphatidylinositol labeling was found inhibited by the assayed cytokines. Our results demonstrate an effect of sepsis-related cytokines, more evident for tumor necrosis factor, on hepatocyte lipid synthesis either from glucose or palmitate. Also, the findings support the hypothesis that cytokine-induced changes in hepatocyte lipid synthesis can contribute to the impairment in lipidic metabolism seen in patients with sepsis.