Specific role of interleukin-1 in hepatic neutrophil recruitment after ischemia/reperfusion
Specific role of interleukin-1 in hepatic neutrophil recruitment after ischemia/reperfusion
复制标题
DOI：
10.1016/s0002-9440(10)64456-2
复制
发表时间：
2002-11-01
影响因子：
6
通讯作者：
Lentsch, AB
中科院分区：
文献类型：
--
作者：
Kato, A;Gabay, C;Lentsch, AB
肝脏缺血/再灌注损伤主要是由再灌注后中性粒细胞募集到肝脏中的产物引起的。负责这种炎症反应发展的介质被认为是肿瘤坏死因子-α和白细胞介素（IL）-1。虽然有大量的证据支持肿瘤坏死因子-α的作用，但对IL-1在这种损伤中的功能知之甚少。在目前的研究中，我们调查是否IL-1是一个关键的介导的诱导肝脏炎症缺血/再灌注后。将野生型和IL-1受体I敲除（IL-1 RI（-/-））小鼠暴露于90分钟的部分肝缺血和长达24小时的再灌注。在野生型小鼠中，IL-1 β表达在缺血和再灌注8小时后达到最大。同时，通过血清丙氨酸转氨酶水平和肝组织病理学评估，野生型和IL-1 RI（-/-）小鼠均存在严重的肝损伤。然而，IL-1 RI（-/-）小鼠肝组织中的中性粒细胞积聚显着减少肝髓过氧化物酶含量和组织学测量。IL-IRI-/-小鼠肝脏中性粒细胞募集减少与转录因子核因子-kappaB活化减少和CXC趋化因子巨噬细胞炎性蛋白-2表达减少相关。这些数据表明，IL-1的功能，以增加中性粒细胞的积累，但不发挥重要作用，在这种反应。
Hepatic ischemia/reperfusion injury is caused primarily by the products of neutrophils recruited into the liver after reperfusion. The mediators responsible for the development of this inflammatory response are thought to be tumor necrosis factor-alpha and interleukin (IL)-1. Although there is abundant evidence to support a role for tumor necrosis factor-alpha, much less is known about the function of IL-1 in this injury. In the present studies, we investigated whether IL-1 was a critical mediator for the induction of liver inflammation after ischemia/reperfusion. Wild-type and IL-1 receptor I-knockout (IL-1RI(-/-)) mice were exposed to 90 minutes of partial hepatic ischemia and up to 24 hours of reperfusion. In wild-type mice, IL-1beta expression was maximal after ischemia and 8 hours of reperfusion. At the same time, both wild-type and IL-1RI(-/-) mice had severe liver injury as assessed by serum alanine aminotransferase levels and hepatic histopathology. However, IL-1RI(-/-) mice had significantly less neutrophil accumulation in liver tissues as measured by liver myeloperoxidase content and histology. The reduction in hepatic neutrophil recruitment in IL-IRI-/- mice was associated with decreased activation of the transcription factor, nuclear factor-kappaB, and reduced expression of the CXC chemokine, macrophage inflammatory protein-2. These data suggest that IL-1 functions to augment neutrophil accumulation, but does not play an essential role in this response.