ENDOTOXEMIA IN HORSES - A REVIEW OF CELLULAR AND HUMORAL MEDIATORS INVOLVED IN ITS PATHOGENESIS
ENDOTOXEMIA IN HORSES - A REVIEW OF CELLULAR AND HUMORAL MEDIATORS INVOLVED IN ITS PATHOGENESIS
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DOI：
10.1111/j.1939-1676.1991.tb00944.x
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发表时间：
1991-05-01
影响因子：
2.6
通讯作者：
MORRIS, DD
中科院分区：
文献类型：
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作者：
MORRIS, DD
内毒素血症仍然是马死亡的主要原因，与引起绞痛和新生马驹败血症的胃肠道疾病的发病机制密切相关。 内毒素通常存在于肠内，通过受损的肠粘膜进入血液，或者当革兰氏阴性微生物在组织中增殖时发生内毒素血症。 内毒素通过单核吞噬细胞系统从循环中去除，单核吞噬细胞对这些脂多糖（LPS）的反应在确定临床疾病的严重程度中起重要作用。 巨噬细胞变得高度活化，以增强LPS的分泌、吞噬和杀灭功能。 巨噬细胞衍生的细胞因子是内毒素血症的许多病理生理后果的原因。 花生四烯酸代谢产物前列环素和血栓素A2可能介导早期血流动力学功能障碍，白三烯可能在内毒素血症期间增强组织缺血。 白细胞介素1（IL-1）诱导发热，并负责炎症级联反应，这构成了急性期反应。 肿瘤坏死因子（TNF）是LPS作用的重要近端介质，其作用是引发影响休克和组织损伤的其他分子的事件和形成。 全身施用TNF产生与内毒素血症相关的大多数生理紊乱，并且针对TNF的抗体显著降低实验动物中LPS诱导的死亡率。 单核吞噬细胞对内毒素的反应是表达促凝血酶原激酶样促凝血活性（PCA），从而引发微血管血栓形成。 IL-1和TNF均诱导PCA表达，为LPS诱导的凝血病创造正反馈回路。 巨噬细胞衍生的血小板活化因子有助于凝血功能障碍并进一步刺激花生四烯酸代谢。 内毒素血症的最终后果是多系统器官衰竭和死亡。 内毒素血症期间介质的众多反馈回路和交织级联挑战简单的治疗方法。 最佳的治疗方法可能包括改变单核吞噬细胞产生炎症介质的方法。
Endotoxemia remains the leading cause of death in horses, being intimately involved in the pathogenesis of gastrointestinal disorders that cause colic and neonatal foal septicemia. Endotoxins, normally present within the bowel, gain access to the blood across damaged intestinal mucosa, or endotoxemia occurs when gram negative organisms proliferate in tissues. Endotoxins are removed from the circulation by the mononuclear phagocyte system, and the response of mononuclear phagocytes to these lipopolysaccharides (LPS) play an important role in determining the severity of clinical disease. Macrophages become highly activated for enhanced secretory, phagocytic and cidal functions by LPS. Macrophage-derived cytokines are responsible for many of the pathophysiologic consequences of endotoxemia. The arachidonic acid metabolites, prostacyclin and thromboxane A2 likely mediate early hemodynamic dysfunction and the leukotrienes may potentiate tissue ischemia during endotoxemia. Interleukin 1 (IL-1) induces fever and is responsible for the inflammatory cascade, which constitutes the acute phase response. Tumor necrosis factor (TNF), an important proximal mediator of the effects of LPS, acts to initiate events and formation of other molecules that affect shock and tissue injury. Systemic administration of TNF produces most of the physiologic derangements that are associated with endotoxemia and antibodies that are directed against TNF significantly reduce LPS-induced mortality in experimental animals. In response to endotoxins, mononuclear phagocytes express thromboplastin-like procoagulant activity (PCA), which initiates microvascular thrombosis. Both Il-1 and TNF induce PCA expression, creating a positive feedback loop for LPS-induced coagulopathy. A macrophage-derived platelet activating factor contributes to coagulation dysfunction and further stimulates arachidonic acid metabolism. The ultimate consequences of endotoxemia are multiple system organ failure and death. The numerous feedback loops and intertwining cascades of mediators during endotoxemia defy simplistic methods of treatment. The optimal therapy likely involves methods to alter the generation of inflammatory mediators by mononuclear phagocytes.