Bemelmans M H, Greve J W, Gouma D J, Buurman W A
Department of Surgery, University of Limburg, Maastricht, Netherlands.
Gut. 1996 Mar;38(3):447-53. doi: 10.1136/gut.38.3.447.
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.
黄疸小鼠体内存在系统性肿瘤坏死因子（TNF）。据报道，两种可溶性TNF受体，即sTNFr-P55和sTNFr-P75在针对TNF的天然防御中发挥作用。本研究调查了黄疸小鼠体内循环TNF和sTNFr的特性。数据显示，这些小鼠体内的TNF无生物学活性，且两种sTNFr均有增加（p < 0.001）。已知黄疸小鼠的手术创伤会伴随高死亡率（36%）和TNF浓度升高。本研究表明，黄疸小鼠手术创伤后系统性TNF和sTNFr浓度均升高，且发现sTNFr浓度而非TNF浓度与死亡率相关。与此发现一致的是，本研究表明，在这些小鼠手术创伤前用乳果糖预处理可显著降低术后sTNFr-P75的浓度（p < 0.005）和死亡率（0%；p < 0.05），而不降低TNF浓度，而抗TNF抗体则无效。总之，这些数据表明，胆汁淤积时TNF会因sTNFr浓度升高而迅速失活。此外，sTNFr浓度而非TNF浓度与梗阻性黄疸手术后的死亡率有良好的相关性。乳果糖对死亡率的积极作用可能是由炎症状态降低所致。
