Effect of sepsis-related cytokines on lipid synthesis by isolated human hepatocytes.

OBJECTIVE

To investigate the effect of tumour necrosis factor-alpha (TNF-alpha) and other sepsis related cytokines on the synthesis of several lipid fractions by human hepatocytes.

DESIGN

Laboratory study.

SETTING

University departments of surgery and biochemistry.

MATERIAL

Livers from eight donors of other organs.

MAIN OUTCOME MEASURES

Effect of TNF-alpha, interleukin-1 (IL-1), and interleukin-6 (IL-6) on the synthesis of triacylglycerol and phospholipids by freshly isolated human hepatocytes.

RESULTS

All three cytokines, particularly TNF-alpha, inhibited the incorporation of D-glucose uniformly labelled with 14C (D-(U-14C) glucose) into phosphatidylcholine. The incorporation of D-(U-14C) glucose into triacylglycerol and free fatty acids was significantly stimulated by TNF-alpha and IL-1, but not by IL-6. When palmitate uniformly labelled with 14C was used as the radiolabelled precursor, TNF-alpha stimulated the synthesis of both triacylglycerol and phosphatidylcholine, neither of which was affected by IL-1 or IL-6.

CONCLUSION

Changes that are induced by cytokines in lipid synthesis by hepatocytes can contribute to the impairment of lipid metabolism seen in septic patients. TNF-alpha seemed to have more effect than the other two cytokines.