Expression of interleukin-18 in the lung after endotoxemia or hemorrhage-induced acute lung injury
Expression of interleukin-18 in the lung after endotoxemia or hemorrhage-induced acute lung injury
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DOI：
10.1165/ajrcmb.22.6.3832
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发表时间：
2000-06-01
影响因子：
6.4
通讯作者：
Abraham, E
中科院分区：
文献类型：
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作者：
Arndt, PG;Fantuzzi, G;Abraham, E
出血和内毒素血症是发生急性肺损伤的重要危险因素。白细胞介素 (IL)-18 是最近描述的一种细胞因子，在 IL-18 前体被 IL-1 转换酶 (ICE) 裂解后，以其成熟的活性形式释放。 IL-18 具有多种免疫调节特性，包括诱导干扰素-γ (IFN-gamma)、IL-1β、肿瘤坏死因子-a 和细胞间粘附分子-1。为了研究 IL-18 在急性肺损伤中的可能参与，我们使用小鼠出血或内毒素血症模型检查了其表达以及 IFN-γ、IL-12 和 ICE 的表达。出血或内毒素血症后，肺中 IL-18 信使 RNA (mRNA) 的量增加。然而，只有内毒素血症与肺和血浆 IL-18 蛋白浓度升高相关。内毒素血症后肺部的 ICE 表达增加，但出血后则没有增加。尽管出血或内毒素血症后肺部 IFN-γ 表达增加，但仅在内毒素血症后才发现肺部 IL-12 mRNA 水平升高。这些结果表明，出血和内毒素血症会诱导肺部不同模式的免疫调节细胞因子表达。特别是，出血或内毒素血症后 ICE 表达的差异可能会影响下游细胞因子活性形式的产生，包括 IL-18。出血后肺部的 IFN-γ 表达似乎通过独立于 IL-12 和 IL-18 的途径发生。 IL-18 可能在调节内毒素血症后急性肺损伤的发展中发挥作用，但在出血后则不然。
Hemorrhage and endotoxemia are important risk factors for the development of acute lung injury. Interleukin (IL)-18 is a recently described cytokine released in its mature, active form after pro-IL-18 is cleaved by the IL-1 converting enzyme (ICE). IL-18 has multiple immunomodulating properties, including induction of interferon-gamma (IFN-gamma), IL-1 beta, tumor necrosis factor-a, and intercellular adhesion molecule-1. To examine the possible involvement of IL-18 in acute lung injury, we examined its expression, as well as that of IFN-gamma, IL-12, and ICE, using murine hemorrhage or endotoxemia models. The amounts of IL-18 messenger RNA (mRNA) increased in the lung after hemorrhage or endotoxemia. However, only endotoxemia was associated with elevations in lung and plasma concentrations of IL-18 protein. ICE expression was increased in the lungs after endotoxemia but not after hemorrhage. Although IFN-gamma expression increased in the lungs after hemorrhage or endotoxemia, elevations in lung IL-12 mRNA levels were found only after endotoxemia. These results indicate that hemorrhage and endotoxemia induce different patterns of immunomodulatory cytokine expression in the lungs. In particular, differences in the expression of ICE after hemorrhage or endotoxemia may affect generation of the active forms of downstream cytokines, including IL-18. IFN-gamma expression in the lungs after hemorrhage appears to occur through a pathway independent of IL-12 and IL-18. IL-18 may play a role in modulating the development of acute lung injury after endotoxemia but not after hemorrhage.