Mikolka Pavol, Kopincova Jana, Kosutova Petra, Kolomaznik Maros, Calkovska Andrea, Mokra Daniela
a Biomedical Center Martin and Department of Physiology , Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava , Martin , Slovakia.
Exp Lung Res. 2018 Feb;44(1):40-50. doi: 10.1080/01902148.2017.1420272. Epub 2018 Jan 11.
Meconium aspiration syndrome (MAS) is life-threatening respiratory failure of newborns which can be treated by exogenous surfactant. In response to meconium, increased levels of chemokine IL-8 (CXCL8) stimulate massive neutrophil infiltration of the lungs. Local accumulation and activation of neutrophils, on-going inflammation, lung edema, and oxidative damage contribute to inactivation of endogenous and therapeutically given surfactants. Therefore, we have hypothesized that addition of monoclonal anti-IL-8 antibody into exogenous surfactant can mitigate the neutrophil-induced local injury and the secondary surfactant inactivation and may finally result in improvement of respiratory functions.
New Zealand rabbits with intratracheal meconium-induced respiratory failure (meconium 25 mg/ml, 4 ml/kg) were divided into three groups: untreated (M), surfactant-treated (M + S), and treated with combination of surfactant and anti-IL-8 antibody (M + S + anti-IL-8). Surfactant therapy consisted of two lung lavages with diluted porcine surfactant Curosurf (10 ml/kg, 5 mg phospholipids (PL)/ml) followed by undiluted Curosurf (100 mg PL/kg) delivered by means of asymmetric high-frequency jet ventilation (f. 300/min, Ti 20%). In M + S + anti-IL-8 group, anti-IL-8 antibody (100 µg/kg) was added directly to Curosurf dose. Animals were oxygen-ventilated for additional 5 h, respiratory parameters were measured regularly. Subsequently, cell counts in bronchoalveolar lavage fluid (BAL), lung edema formation, oxidative damage, levels of interleukins (IL)-1β and IL-6 in the lung homogenate were evaluated.
Surfactant instillation significantly improved lung function. Addition of anti-IL-8 to surfactant further improved gas exchange and ventilation efficiency and had longer-lasting effect than surfactant-only therapy. Combined treatment showed the trend to reduce neutrophil count in BAL fluid, local oxidative damage, and levels of IL-1β and IL-6 more effectively than surfactant-alone, however, these differences were not significant.
Addition of anti-IL-8 antibody to surfactant could potentiate the efficacy of Curosurf on the gas exchange in experimental model of MAS.
胎粪吸入综合征（MAS）是危及新生儿生命的呼吸衰竭，可通过外源性表面活性剂进行治疗。针对胎粪，趋化因子白细胞介素-8（CXCL8）水平升高会刺激大量中性粒细胞浸润肺部。中性粒细胞的局部聚集和活化、持续的炎症、肺水肿以及氧化损伤会导致内源性和治疗性给予的表面活性剂失活。因此，我们推测在外源性表面活性剂中添加单克隆抗白细胞介素-8抗体可以减轻中性粒细胞诱导的局部损伤和继发性表面活性剂失活，并最终可能改善呼吸功能。
将经气管内注入胎粪诱导呼吸衰竭的新西兰兔（胎粪25mg/ml，4ml/kg）分为三组：未治疗组（M）、表面活性剂治疗组（M+S）和表面活性剂与抗白细胞介素-8抗体联合治疗组（M+S+抗白细胞介素-8）。表面活性剂治疗包括用稀释的猪表面活性剂珂立苏（10ml/kg，5mg磷脂（PL）/ml）进行两次肺灌洗，然后通过非对称高频喷射通气（频率300次/分钟，吸气时间20%）给予未稀释的珂立苏（100mg PL/kg）。在M+S+抗白细胞介素-8组中，将抗白细胞介素-8抗体（100μg/kg）直接添加到珂立苏剂量中。动物再进行5小时的氧通气，定期测量呼吸参数。随后，评估支气管肺泡灌洗液（BAL）中的细胞计数、肺水肿形成、氧化损伤、肺匀浆中白细胞介素（IL）-1β和IL-6的水平。
注入表面活性剂显著改善了肺功能。在表面活性剂中添加抗白细胞介素-8进一步改善了气体交换和通气效率，且比单纯表面活性剂治疗具有更持久的效果。联合治疗显示出比单独使用表面活性剂更有效地降低BAL液中中性粒细胞计数、局部氧化损伤以及IL-1β和IL-6水平的趋势，然而，这些差异并不显著。
在表面活性剂中添加抗白细胞介素-8抗体可增强珂立苏在MAS实验模型中对气体交换的疗效。
