Inhaled IL-10 reduces biotrauma and mortality in a model of ventilator-induced lung injury
Inhaled IL-10 reduces biotrauma and mortality in a model of ventilator-induced lung injury
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DOI：
10.1016/j.rmed.2008.09.020
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发表时间：
2009-03-01
影响因子：
4.3
通讯作者：
Hofstetter, Christian
中科院分区：
文献类型：
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作者：
Hoegl, Sandra;Boost, Kim A.;Hofstetter, Christian
背景：高压通气可引起气压伤和肺部炎症，从而导致呼吸机相关性肺损伤（VILI）。通过限制肺动脉。抗炎细胞因子白细胞介素（IL）-10可能具有保护作用。方法：将36只SD大鼠随机分为3组，每组10只，每组10只（每组n = 9）：假手术：压力控制通气，p（max）= 20 cmH（2）O，PEEP = 4; VILI：将呼吸机设置改变20分钟，p（max）= 45 cmH（2）O，PEEP = 0; IL-10（高）：在诱导VILI之前吸入10 μ g/kg IL-10;和IL-10（低）：在诱导VILI之前吸入1 μ g/kg IL-10。结果：高压通气组大鼠支气管肺泡灌洗液（BALF）和血浆中巨噬细胞炎性蛋白（MIP-2）和白细胞介素1 β（IL-1 β）浓度均明显升高。吸入IL-10（10 μ g/kg）可降低这种作用。此外，IL-10增加了动物的存活时间（78%对22%的4小时死亡率），并减少了体外培养的肺泡巨噬细胞的NO释放。此外，IL-10气雾剂以剂量依赖性方式降低VILI诱导的肺热休克蛋白-70表达。同样，基质金属蛋白酶（MMP）-9在BALF中的激活减少剂量依赖性的IL-10。IL-10治疗的动物表现出塔宏观肺损伤评分和肺的完整性和气体exchanges.Conclusions：预防性吸入IL-10改善生存，减少肺损伤实验VILI。结果表明，这种作用可能是通过抑制应激性炎症反应和肺生物损伤而实现的。(C)2008爱思唯尔有限公司保留所有权利。
Background: High-pressure ventilation induces barotrauma and pulmonary inflammation, thus leading to ventilator-induced lung injury (VILI). By limiting the pulmonal. inflammation cascade the anti-inflammatory cytokine interleukin (IL)-10 may have protective effects. Via inhalation, IL-10 reaches the pulmonary system directly and in high concentrations.Methods: Thirty six mate, anesthetized and mechanically ventilated Sprague-Dawley rats were randomly assigned to the following groups (n = 9, each): SHAM: pressure controlled ventilation with p(max) = 20 cmH(2)O, PEEP = 4; VILI: ventilator settings were changed for 20 min to p(max) = 45 cmH(2)O, PEEP = 0; IL-10(high): inhalation of 10 mu g/kg IL-10 prior to induction of VILI; and IL-10(low): inhalation of 1 mu g/kg IL-10 prior to induction of VILI. All groups were ventilated and observed for 4 h.Results: High-pressure ventilation increased the concentrations of macrophage inflammatory protein (MIP)-2 and IL-1 beta in bronchoalveolar lavage fluid (BALF) and plasma. This effect was reduced by the inhalation of IL-10 (10 mu g/kg). Additionally, IL-10 increased the animal survival time (78% vs. 22% 4-h mortality rate) and reduced NO-release from ex vivo cultured alveolar macrophages. Moreover, VILI-induced pulmonary heat shock protein-70 expression was reduced by IL-10 aerosol in a dose-dependent manner. Similarly, the activation of matrix metalloproteinase (MMP)-9 in BALF was reduced dose-dependently by IL-10. IL-10-treated animals showed a tower macroscopic lung injury score and less impairment of lung integrity and gas exchange.Conclusions: Prophylactic inhalation of IL-10 improved survival and reduced lung injury in experimental VILI. Results indicate that this effect maybe mediated by the inhibition of stress-induced inflammation and pulmonary biotrauma. (C) 2008 Elsevier Ltd. All rights reserved.