Increased concentrations of tumour necrosis factor (TNF) and soluble TNF receptors in biliary obstruction in mice; soluble TNF receptors as prognostic factors for mortality

Abstract

Systemic tumour necrosis factor (TNF) is present in jaundiced mice. Two soluble TNF receptors, sTNFr-P55 and sTNFr-P75 are reported to play a part in the natural defence against TNF. This study investigated the properties of circulating TNF and sTNFr in jaundiced mice. The data show that TNF in these mice is biologically inactive and that an increase of both sTNFr is seen (p < 0.001). Surgical trauma in jaundiced mice is known to be accompanied by a high mortality (36%) and increased TNF concentrations. This study shows that both systemic TNF and sTNFr concentrations are increased after surgical trauma in jaundiced mice and that sTNFr concentrations rather than TNF concentrations were found to be correlated with mortality. In line with this finding this study showed that lactulose pretreatment before a surgical trauma in these mice significantly reduces postoperative concentrations of sTNFr-P75 (p < 0.005) and mortality (0%; p < 0.05) without reducing TNF concentrations, while anti-TNF antibodies were ineffective. In conclusion, these data suggest that TNF in biliary obstruction is rapidly inactivated by increased concentrations of sTNFr. Furthermore, sTNFr concentrations rather than TNF concentrations show a good correlation with mortality after surgery in obstructive jaundice. The positive effect of lactulose on mortality could be caused by a decreased inflammatory status.