Preoperative oral treatment with lactulose is used to prevent complications after surgery in patients with obstructive jaundice. The effect is perhaps the result of an inactivation of gut derived endotoxins but the exact mechanism of action is, however, unknown. Tumour necrosis factor is an important mediator of endotoxin toxicity. The cytokine tumour necrosis factor is mainly produced by mononuclear phagocytes. In this study, the effect of lactulose on the endotoxin induced tumour necrosis factor release by monocytes was investigated. The direct effect of lactulose on endotoxin was tested in a chromogenic limulus amoebocyte lysate assay. Polymyxin B a known inactivator of endotoxin was used as control in both experiments. Lactulose has a limited capacity to inactivate endotoxin as measured in the endotoxin assay. In contrast lactulose significantly reduced endotoxin induced tumour necrosis factor production by monocytes. In conclusion lactulose inhibits tumour necrosis factor production by a direct inhibitory effect on monocytes, rather than by inactivation of endotoxin. Because tumour necrosis factor is an important mediator of endotoxin toxicity, this inhibitory effect could explain the beneficial effect of lactulose in obstructive jaundice.
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