ACID ASPIRATION-INDUCED LUNG INJURY IN RABBITS IS MEDIATED BY INTERLEUKIN-8-DEPENDENT MECHANISMS
ACID ASPIRATION-INDUCED LUNG INJURY IN RABBITS IS MEDIATED BY INTERLEUKIN-8-DEPENDENT MECHANISMS
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DOI：
10.1172/jci118009
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发表时间：
1995-07-01
影响因子：
15.9
通讯作者：
BROADDUS, VC
中科院分区：
文献类型：
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作者：
FOLKESSON, HG;MATTHAY, MA;BROADDUS, VC
酸吸入性肺损伤可能主要由中性粒细胞通过酸诱导的细胞因子募集到肺中介导。我们假设，一个主要的酸诱导的细胞因子是IL-8和中和抗兔IL-8单克隆抗体（ARIL8.2）将减轻酸诱导的肺损伤的兔子。将盐酸（pH = 1.5，溶于1/3生理盐水中）或1/3生理盐水（4 ml/kg）滴入通气麻醉家兔的肺中。对家兔进行6或24 h研究。在没有抗IL-8单克隆抗体的酸滴注兔中，在最初的6 h内发生严重的肺损伤;在长期实验中，所有兔在12 - 14 h内死亡，并伴有肺损伤。在给予抗IL-8单克隆抗体的酸滴注家兔中，（2 mg/kg，静脉注射），或作为预处理（酸前5分钟）或作为处理（酸后1小时），酸诱导的氧合和血管外肺水异常得到预防，血管外蛋白质积累减少70%;在长期实验中，抗IL-8治疗在整个24小时期间类似地保护肺功能。抗IL-8单克隆抗体还显著降低了空气空间中性粒细胞计数和IL-8浓度。本研究确定IL-8是酸诱导的肺损伤发展的关键细胞因子。IL-8的中和可能为这种临床上重要形式的急性肺损伤提供第一种有用的治疗。
Acid aspiration lung injury may be mediated primarily by neutrophils recruited to the lung by acid-induced cytokines. We hypothesized that a major acid-induced cytokine was IL-8 and that a neutralizing anti-rabbit-IL-8 monoclonal antibody (ARIL8.2) would attenuate acid-induced lung injury in rabbits. Hydrochloric acid (pH = 1.5 in 1/3 normal saline) or 1/3 normal saline (4 ml/kg) was instilled into the lungs of ventilated, anesthetized rabbits. The rabbits were studied for 6 or 24 h. In acid-instilled rabbits without the anti-IL-8 monoclonal antibody, severe lung injury developed in the first 6 h; in the long-term experiments, all rabbits died with lung injury between 12 and 14 h. In acid-instilled rabbits given the anti-IL-8 monoclonal antibody (2 mg/kg, intravenously) either as pretreatment (5 min before the acid) or as treatment (1 h after the acid), acid-induced abnormalities in oxygenation and extravascular lung water were prevented and extravascular protein accumulation was reduced by 70%; in the long-term experiments, anti-IL-8 treatment similarly protected lung function throughout the 24-h period. The anti-IL-8 monoclonal antibody also significantly reduced air space neutrophil counts and IL-8 concentrations. This study establishes IL-8 as a critical cytokine for the development of acid-induced lung injury. Neutralization of IL-8 may provide the first useful therapy for this clinically important form of acute lung injury.