Belov L, Meher-Homji V, Putaswamy V, Miller R
Institute for Immunology and Allergy Research, Westmead, New South Wales, Australia.
Immunol Cell Biol. 1999 Feb;77(1):34-40. doi: 10.1046/j.1440-1711.1999.00796.x.
Septic shock or systemic inflammatory response syndrome (SIRS) often develops in patients following burns, traumatic injury, surgery or biliary obstruction. Although the inflammatory cytokines TNF-alpha and IL-1 have been strongly implicated in the development of these syndromes, treatment of patients by the systemic administration of inhibitors of TNF-alpha or IL-1 has shown limited effectiveness. Recent reports suggest that septic shock may be perpetuated by inflammatory cytokines secreted by the liver in response to bacterial translocation resulting from cytokine-induced gastrointestinal damage. The present study sought to demonstrate the presence of high levels of inflammatory cytokines in the bile or small intestine of patients suffering from septic shock or SIRS, with a view to the development of strategies for the reduction of gastrointestinal damage through intraduodenal administration of cytokine inhibitors. Western blot analysis of human bile or intestinal fluid using anti-TNF-alpha antibodies resulted in the detection of a number of bands in samples from patients with septic shock or SIRS. However, these proteins differed antigenically from human recombinant TNF-alpha (rTNF-alpha) and showed no activity in a biological assay for TNF-alpha. Antibodies to IL-1 alpha and IL-1 beta detected several strong bands, some of which appeared to be identical to recombinant IL-1 alpha and IL-1 beta. It is concluded that proteins resembling several known inflammatory cytokines are present in the bile and intestine of septic shock patients, but it is suggested that further work is required to determine the nature and function of these molecules.
脓毒性休克或全身炎症反应综合征(SIRS)常发生于烧伤、创伤、手术后或胆道梗阻后的患者。尽管炎性细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-1(IL-1)与这些综合征的发生密切相关,但通过全身给予TNF-α或IL-1抑制剂来治疗患者的效果有限。最近的报告表明,脓毒性休克可能因肝脏分泌的炎性细胞因子而持续存在,这些细胞因子是对细胞因子诱导的胃肠道损伤导致的细菌移位做出的反应。本研究旨在证明脓毒性休克或SIRS患者的胆汁或小肠中存在高水平的炎性细胞因子,以期通过十二指肠内给予细胞因子抑制剂来制定减少胃肠道损伤的策略。使用抗TNF-α抗体对人胆汁或肠液进行蛋白质印迹分析,在脓毒性休克或SIRS患者的样本中检测到多个条带。然而,这些蛋白质在抗原性上与重组人TNF-α(rTNF-α)不同,并且在TNF-α的生物学检测中无活性。抗IL-1α和IL-1β抗体检测到几条强条带,其中一些似乎与重组IL-1α和IL-1β相同。结论是,脓毒性休克患者的胆汁和肠道中存在类似于几种已知炎性细胞因子的蛋白质,但建议需要进一步研究以确定这些分子的性质和功能。