In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury
In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury
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DOI：
10.1136/thx.2006.059410
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发表时间：
2007-01-01
期刊：
影响因子：
10
通讯作者：
Thickett, D. R.
中科院分区：
文献类型：
--
作者：
Perkins, G. D.;Nathani, N.;Thickett, D. R.
背景：静脉注射沙丁胺醇(沙丁胺醇)可减少急性呼吸窘迫综合征(ARDS)患者的肺水。目的：探讨沙丁胺醇对中性粒细胞功能的影响。方法：体外测定沙丁胺醇对中性粒细胞功能的影响。收集35例急性肺损伤(ALI)/ARDS患者、14例ARDS高危患者和7例机械通气对照组(ALI/ARDS组)基线及应用安慰剂或沙丁胺醇治疗4d后的血和支气管肺泡灌洗液(BAL)。用热稀释法(PICCO)测定肺泡毛细血管通透性。结果：生理浓度的沙丁胺醇在体外对中性粒细胞的趋化能力、存活率及细胞凋亡率均无影响。ALI/ARDS患者与高危患者和呼吸机对照组相比，中性粒细胞活化和黏附分子表达增加。肺泡毛细血管通透性与肺泡灌洗髓过氧化物酶(r=0.40，p=0.038)、肺泡灌洗液白细胞介素8(r=0.38，p=0.033)呈正相关。在ALI/ARDS患者中，沙丁胺醇增加了循环中中性粒细胞的数量，但对肺泡中性粒细胞无影响。结论：在ALI/ARDS发病时，中性粒细胞募集和激活增加。生理浓度的沙丁胺醇在体外不改变中性粒细胞的趋化能力、存活率或凋亡率。在体内，沙丁胺醇增加了循环中的中性粒细胞，但对肺泡中性粒细胞或中性粒细胞的激活没有影响。这些数据表明，沙丁胺醇减少肺水的有益作用与调节中性粒细胞依赖的炎症途径无关。
Background: Intravenous salbutamol (albuterol) reduces lung water in patients with the acute respiratory distress syndrome (ARDS). Experimental data show that it also reduces pulmonary neutrophil accumulation or activation and inflammation in ARDS.Aim: To investigate the effects of salbutamol on neutrophil function.Methods: The in vitro effects of salbutamol on neutrophil function were determined. Blood and bronchoalveolar lavage (BAL) fluid were collected from 35 patients with acute lung injury (ALI)/ARDS, 14 patients at risk from ARDS and 7 ventilated controls at baseline and after 4 days' treatment with placebo or salbutamol (ALI/ARDS group). Alveolar-capillary permeability was measured in vivo by thermodilution (PiCCO). Neutrophil activation, adhesion molecule expression and inflammatory cytokines were measured.Results: In vitro, physiological concentrations of salbutamol had no effect on neutrophil chemotaxis, viability or apoptosis. Patients with ALI/ARDS showed increased neutrophil activation and adhesion molecule expression compared with at risk-patients and ventilated controls. There were associations between alveolar capillary permeability and BAL myeloperoxidase (r = 0.4, p = 0.038) and BAL interleukin 8 (r = 0.38, p = 0.033). In patients with ALI/ARDS, salbutamol increased numbers of circulating neutrophils but had no effect on alveolar neutrophils.Conclusion: At the onset of ALI/ARDS, there is increased neutrophil recruitment and activation. Physiological concentrations of salbutamol did not alter neutrophil chemotaxis, viability or apoptosis in vitro. In vivo, salbutamol increased circulating neutrophils, but had no effect on alveolar neutrophils or on neutrophil activation. These data suggest that the beneficial effects of salbutamol in reducing lung water are unrelated to modulation of neutrophil-dependent inflammatory pathways.