The role of proinflammatory cytokines in lung ischemia-reperfusion injury
The role of proinflammatory cytokines in lung ischemia-reperfusion injury
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DOI：
10.1067/mtc.2003.16
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发表时间：
2003-02-01
影响因子：
6
通讯作者：
Mulligan, MS
中科院分区：
文献类型：
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作者：
Krishnadasan, B;Naidu, BV;Mulligan, MS
目的：促炎细胞因子在心脏、肾脏、小肠、皮肤和肝脏的缺血再灌注损伤中起重要作用。目前对它们在肺缺血再灌注损伤中的作用知之甚少。本研究旨在探讨肿瘤坏死因子α和白介素1β在肺缺血再灌注损伤中的作用。方法：雄性大鼠左肺缺血90min，再灌流4h。治疗组动物在再灌注前接受抗肿瘤坏死因子a或抗白介素1β抗体治疗。用125碘标记的牛血清白蛋白测定肺血管通透性的增加。根据肺实质的活动性来确定中性粒细胞在肺实质中的隔离。进行支气管肺泡灌洗以测量细胞计数。结果：抗肿瘤坏死因子α和抗白介素1β组动物的损伤程度明显低于阳性对照组(血管通透性分别降低48.7%和29.4%；P<；.001)。联合应用抗肿瘤坏死因子α抗体和白介素1βX可减少71%的血管损伤。在接受抗肿瘤坏死因子a和抗白细胞介素1β(髓过氧化物酶含量分别降低30.9%和38.5%；P<；.04)和联合阻断的动物中，肺内中性粒细胞聚集明显减少(P<；.01)，保护作用更强(P<；.01)。经抗肿瘤坏死因子a、抗白介素1β及联合治疗后，支气管肺泡灌洗液中的白细胞含量也降低。通透性、髓过氧化物酶和支气管肺泡灌洗白细胞含量的降低也导致组织学损伤的减少。最后，抗肿瘤坏死因子α和抗白介素1β治疗导致早期反应和调节细胞因子的信使RNA表达减少。结论：肿瘤坏死因子和白介素1β有助于调节肺缺血再灌注损伤的发展。它们似乎通过改变促炎和抗炎细胞因子的表达以及影响组织中性粒细胞的募集来促进损伤。
Objective: Proinflammatory cytokines are known to play roles in ischemia-reperfusion injury of the heart, kidney, small bowel, skin, and liver. Little is known about their roles in ischemia-reperfusion injury of the lung. This study was undertaken to define the role of 2 proinflammatory cytokines, tumor necrosis factor a and interleukin 1beta, in ischemia-reperfusion injury of the lung.Methods: Left lungs of male rats were rendered ischemic for 90 minutes and reperfused for up to 4 hours. Treated animals received anti-tumor necrosis factor a or anti-interleukin 1beta antibody before reperfusion. Increased vascular permeability in the lung was measured by using iodine 125-labeled bovine serum albumin. Neutrophil sequestration in the lung parenchyma was determined on the basis of activity. Bronchoalveolar lavage was performed to measure cell counts. Separate tissue samples were processed for histology, cytokine protein, and messenger RNA content by using Western blotting and the ribonuclease protection assay.Results: Animals receiving anti-tumor necrosis factor a and anti-interleukin 1beta demonstrated reduced injury compared with that seen in positive control animals (vascular permeability of 48.7% and 29.4% lower, respectively; P < .001). Vascular injury was reduced by 71% when antibodies to tumor necrosis factor a and interleukin 1betaX were administered together. Lung neutrophil accumulation was markedly reduced among animals receiving anti-tumor necrosis factor a and anti-interleukin 1beta (myeloperoxidase content of 30.9% and 38.5% lower, respectively; P < .04) and combination blockade afforded even greater protection (52.4% decrease, P < .01). Bronchoalveolar lavage leukocyte content was also reduced by treatment with anti-tumor necrosis factor a, anti-interleukin 1beta, and combination treatment. Reductions in permeability, myeloperoxidase, and bronchoalveolar lavage leukocyte content also resulted in a decrease in a histologic injury. Finally, anti-tumor necrosis factor alpha and anti-interleukin 1beta treatment resulted in decreased messenger RNA expression for a number of early response and regulatory cytokines.Conclusion: Tumor necrosis factor a and interleukin 1beta help regulate the development of lung ischemia-reperfusion injury. They appear to promote injury by altering expression of proinflammatory and anti-inflammatory cytokines and influencing tissue neutrophil recruitment.