Acute alcohol intoxication increases interleukin-18-mediated neutrophil infiltration and lung inflammation following burn injury in rats
Acute alcohol intoxication increases interleukin-18-mediated neutrophil infiltration and lung inflammation following burn injury in rats
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DOI：
10.1152/ajplung.00408.2006
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发表时间：
2007-05-01
影响因子：
4.9
通讯作者：
Choudhry, Mashkoor A.
中科院分区：
文献类型：
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作者：
Li, Xiaoling;Kovacs, Elizabeth J.;Choudhry, Mashkoor A.
在这项研究中，我们研究了IL-18是否在酒精（EtOH）和烧伤后的肺部炎症中发挥作用。在烧伤或假损伤之前，用EtOH管饲雄性大鼠（类似于250 g），以达到类似于100 mg/dl的血液EtOH水平（类似于12.5%的总体表面积）。损伤后立即用载体、半胱天冬酶-1抑制剂AC-YVAD-CHO处理大鼠以阻断IL-18产生或用IL-18中和抗IL-18抗体处理大鼠。在另一组中，用与损伤前16 h相似的抗中性粒细胞抗血清处理大鼠，以消耗中性粒细胞。在损伤后第1天，肺组织IL- 18、中性粒细胞趋化因子（CINC-1/CINC-3）、ICAM-1、中性粒细胞浸润、MPO活性和水含量（即，与单独接受EtOH中毒或烧伤的大鼠相比，在接受EtOH和烧伤联合损伤的大鼠中，水肿）显著增加。Caspase-1抑制剂治疗大鼠可防止EtOH和烧伤后肺组织IL-18、CINC-1、CINC-3、ICAM-1、MPO活性的增加和水肿。在用抗IL-18抗体处理的大鼠中，肺IL-18、MPO和水肿的增加也被阻止。此外，抗中性粒细胞抗血清的管理也减弱了肺MPO活性和水肿的增加，但不能防止乙醇和烧伤后IL-18水平的增加。这些发现表明，烧伤前急性乙醇中毒上调IL-18，这反过来又有助于增加中性粒细胞浸润。此外，中性粒细胞的存在似乎是关键的IL-18介导的增加肺组织水肿后，联合损害的乙醇和烧伤。
In this study, we examined whether IL-18 plays a role in lung inflammation following alcohol ( EtOH) and burn injury. Male rats (similar to 250 g) were gavaged with EtOH to achieve a blood EtOH level of similar to 100 mg/dl before burn or sham injury (similar to 12.5% total body surface area). Immediately after injury, rats were treated with vehicle, caspase-1 inhibitor AC-YVAD-CHO to block IL-18 production or with IL-18 neutralizing anti-IL-18 antibodies. In another group, rats were treated with anti-neutrophil antiserum similar to 16 h before injury to deplete neutrophils. On day 1 after injury, lung tissue IL- 18, neutrophil chemokines (CINC-1/CINC-3), ICAM-1, neutrophil infiltration, MPO activity, and water content (i.e., edema) were significantly increased in rats receiving a combined insult of EtOH and burn injury compared with rats receiving either EtOH intoxication or burn injury alone. Treatment of rats with caspase-1 inhibitor prevented the increase in lung tissue IL-18, CINC-1, CINC-3, ICAM-1, MPO activity, and edema following EtOH and burn injury. The increase in lung IL-18, MPO, and edema was also prevented in rats treated with anti-IL-18 antibodies. Furthermore, administration of anti-neutrophil antiserum also attenuated the increase in lung MPO activity and edema, but did not prevent the increase in IL-18 levels following EtOH and burn injury. These findings suggest that acute EtOH intoxication before burn injury upregulates IL-18, which in turn contributes to increased neutrophil infiltration. Furthermore, the presence of neutrophils appears to be critical for IL-18-meditaed increased lung tissue edema following a combined insult of EtOH and burn injury.