Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice.
Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice.
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DOI：
10.1371/journal.pone.0061405
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Faubel S
中科院分区：
文献类型：
--
作者：
Bhargava R;Janssen W;Altmann C;Andrés-Hernando A;Okamura K;Vandivier RW;Ahuja N;Faubel S
急性呼吸窘迫综合征(ARDS)患者血清和支气管肺泡液中IL-6水平升高预示着机械通气时间延长和预后不良，但肺泡内IL-6在间接肺损伤中的作用尚不清楚。我们研究了内源性和外源性IL-6在AKI介导的肺损伤(间接肺损伤)、腹腔内(IP)内毒素注射(间接肺损伤)和气管内(IT)内毒素注射(直接肺损伤)中的作用，并假设IL-6在这些急性肺炎症的原因中发挥促炎作用。对成年雄性C57BL/6小鼠进行肺组织炎症(肺组织细胞因子、髓过氧化物酶活性[中性粒细胞浸润的生化标志物])、血清细胞因子(IL-6、CXCL-1、肿瘤坏死因子-α、IL-1β和IL-10)、肺泡灌洗液中中性粒细胞、血清细胞因子的检测。AKI、IP内毒素和IT内毒素后肺组织炎症反应相似。IL-6在IT内毒素后显著升高，而在AKI或IP内毒素后无明显升高。出乎意料的是，IT IL-6在健康小鼠身上发挥了抗炎作用，其特征是BAL液中细胞因子减少。IT IL-6对IT内毒素也有抗炎作用，表现为BAL液细胞因子减少和肺组织炎症；IT IL-6对AKI或IP内毒素肺组织炎症无明显影响。IL-6在IT内毒素所致的直接肺损伤中具有抗炎作用，但在AKI或IP内毒素所致的间接肺损伤的发病机制和治疗中没有作用。由于肺泡内炎症在肺部炎症的直接而非间接原因的发病机制中起重要作用，IT抗炎治疗可能在ARDS的直接原因中发挥作用，但不是间接原因。
Serum and bronchoalveolar fluid IL-6 are increased in patients with acute respiratory distress syndrome (ARDS) and predict prolonged mechanical ventilation and poor outcomes, although the role of intra-alveolar IL-6 in indirect lung injury is unknown. We investigated the role of endogenous and exogenous intra-alveolar IL-6 in AKI-mediated lung injury (indirect lung injury), intraperitoneal (IP) endotoxin administration (indirect lung injury) and, for comparison, intratracheal (IT) endotoxin administration (direct lung injury) with the hypothesis that IL-6 would exert a pro-inflammatory effect in these causes of acute lung inflammation. Bronchoalveolar cytokines (IL-6, CXCL1, TNF-α, IL-1β, and IL-10), BAL fluid neutrophils, lung inflammation (lung cytokines, MPO activity [a biochemical marker of neutrophil infiltration]), and serum cytokines were determined in adult male C57Bl/6 mice with no intervention or 4 hours after ischemic AKI (22 minutes of renal pedicle clamping), IP endotoxin (10 µg), or IT endotoxin (80 µg) with and without intratracheal (IT) IL-6 (25 ng or 200 ng) treatment. Lung inflammation was similar after AKI, IP endotoxin, and IT endotoxin. BAL fluid IL-6 was markedly increased after IT endotoxin, and not increased after AKI or IP endotoxin. Unexpectedly, IT IL-6 exerted an anti-inflammatory effect in healthy mice characterized by reduced BAL fluid cytokines. IT IL-6 also exerted an anti-inflammatory effect in IT endotoxin characterized by reduced BAL fluid cytokines and lung inflammation; IT IL-6 had no effect on lung inflammation in AKI or IP endotoxin. IL-6 exerts an anti-inflammatory effect in direct lung injury from IT endotoxin, yet has no role in the pathogenesis or treatment of indirect lung injury from AKI or IP endotoxin. Since intra-alveolar inflammation is important in the pathogenesis of direct, but not indirect, causes of lung inflammation, IT anti-inflammatory treatments may have a role in direct, but not indirect, causes of ARDS.
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DOI：
10.1164/ajrccm.155.5.9154894
发表时间：
1997-05-01
影响因子：
24.7
作者：
Krause, A;Hohberg, B;Witt, C
通讯作者：
Witt, C
影响因子：
8.8
作者：
Metnitz, PGH;Krenn, CG;Druml, W
通讯作者：
Druml, W
影响因子：
9.6
作者：
Kobayashi, A;Hashimoto, S;Ashihara, T
通讯作者：
Ashihara, T
DOI：
10.1164/rccm.200208-966ws
发表时间：
2003-04-01
影响因子：
24.7
作者：
Matthay, MA;Zimmerman, GA;Harabin, AL
通讯作者：
Harabin, AL
DOI：
10.1186/cc7940
发表时间：
2009
期刊：
Critical care (London, England)
影响因子：
--
作者：
Liu KD;Altmann C;Smits G;Krawczeski CD;Edelstein CL;Devarajan P;Faubel S
通讯作者：
Faubel S