Matuschak G M
Department of Internal Medicine, St. Louis University School of Medicine, MO.
New Horiz. 1994 Nov;2(4):488-504.
Organ interactions are increasingly recognized as key determinants of the pathogenesis and potential for resolution of tissue injury during critical illness. A paradigm for a systems model that takes into account the modulatory effects of organ interactions and incorporates the expanding number of molecular and cellular pro-inflammatory networks is still lacking. Unifying hypotheses for multiple organ dysfunction during the systemic inflammatory response syndrome have been slow to emerge. The liver plays a central role in the regulation of multiple host defense, immunologic, biochemical, and metabolic functions during sepsis and trauma. However, the liver is relatively inaccessible for clinical study and its function is often non-specifically defined. Consequently, the liver's pathogenetic importance within a regulatory network of mediator and organ interactions during inflammatory responses leading to acute lung injury is poorly appreciated. This review addresses the concept that hepatic performance, broadly defined, represents a point of convergence in which four regulatory elements of the acute inflammatory response interact over a host defense continuum to affect lung function. These regulatory elements include: a) control of systemic endotoxemia, bacteremia, and vasoactive by-products of sepsis and trauma by the gut-liver axis of inflammation, mononuclear phagocytic clearance, and Fc and complement receptor-mediated events; b) production and export of endogenous cytokine and eicosanoid mediators by Kupffer cells, especially in relation to changes in the prevailing hepatic oxygen supply; c) metabolic inactivation and detoxification of such mediators via cell-to-cell interactions at the Kupffer cell-hepatocyte interface; and d) cytokine-driven synthesis of acute-phase proteins that critically modulate metabolism and inflammation. Our goal is to summarize and integrate recent information that sheds light on mechanisms by which hepatic function modulates host defense homeostasis, thereby influencing pulmonary function in the adult respiratory distress syndrome. Liver-lung interactions are presented as a heuristic paradigm of organ interactions that dynamically modulate systemic immunophysiologic responses during critical illness.
器官间的相互作用日益被视为危重病期间组织损伤发病机制及恢复潜力的关键决定因素。目前仍缺乏一个系统模型范例，该范例既要考虑器官间相互作用的调节效应，又要纳入越来越多的分子和细胞促炎网络。关于全身炎症反应综合征期间多器官功能障碍的统一假说迟迟未能出现。在脓毒症和创伤期间，肝脏在多种宿主防御、免疫、生化和代谢功能的调节中发挥着核心作用。然而，肝脏相对难以进行临床研究，其功能常常未得到明确界定。因此，在导致急性肺损伤的炎症反应中，肝脏在介质和器官相互作用调节网络中的致病重要性未得到充分认识。本综述探讨了这样一个概念，即广义定义的肝脏功能表现代表了一个汇聚点，急性炎症反应的四个调节要素在宿主防御连续过程中相互作用，从而影响肺功能。这些调节要素包括：a）通过炎症的肠 - 肝轴、单核吞噬细胞清除以及Fc和补体受体介导的事件，控制全身内毒素血症、菌血症以及脓毒症和创伤的血管活性副产物；b）库普弗细胞产生并输出内源性细胞因子和类花生酸介质，尤其是与当前肝脏氧供应变化相关的介质；c）通过库普弗细胞 - 肝细胞界面的细胞间相互作用对这些介质进行代谢失活和解毒；d）细胞因子驱动的急性期蛋白合成，这些蛋白对代谢和炎症进行关键调节。我们的目标是总结并整合近期信息，以阐明肝脏功能调节宿主防御稳态从而影响成人呼吸窘迫综合征肺功能的机制。肝 - 肺相互作用被视为器官相互作用的一种启发式范例，它在危重病期间动态调节全身免疫生理反应。
