Acute respiratory distress syndrome following an acute lung injury (ALI) is a life threatening inflammatory condition predominantly characterized by vascular protein leakage, neutrophil recruitment and overexpression of proinflammatory cytokines. Pulmonary and systemic bacterial infections are the major cause of ALI wherein the bacterial cell components play a crucial role. Macrolide/ketolide antibiotics are reported to possess immunomodulatory activity; as a result improved survival has been noted in pneumonia patients. Hence immunomodulatory activity of nafithromycin, a novel lactone ketolide antibacterial agent was assessed in the murine LPS induced ALI model. Vehicle, nafithromycin (100 mg/kg), azithromycin (600 mg/kg) and dexamethasone (20 mg/kg) were administered orally, 1 h prior to LPS challenge and bronchoalveolar lavage (BAL) fluid was collected thereafter at 18, 24 and 48 h to determine the total cell count, total protein, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α and interleukin (IL)-6. Results from the current study showed that pretreatment with nafithromycin significantly reduced the total cell count, total protein, MPO, TNF-α and IL-6 levels in BAL fluid compared to LPS control group. Histopathological evaluations also suggest significant reduction in neutrophil infiltration by nafithromycin. Dexamethasone, a positive reference standard as expected exhibited potent anti-inflammatory activity. The immunomodulatory effect of nafithromycin at dose of 100 mg/kg was comparable to azithromycin dosed at 600 mg/kg. As a result of immunomodulatory activity, nafithromycin is expected to provide additional clinical benefits by resolving the secondary complications associated with severe pneumonia and thereby improving survival in such patients.

中文翻译：

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萘霉素预处理减轻小鼠脂多糖诱导的急性肺损伤的炎症反应

急性肺损伤 (ALI) 后的急性呼吸窘迫综合征是一种危及生命的炎症性疾病，其主要特征是血管蛋白渗漏、中性粒细胞募集和促炎细胞因子的过度表达。肺部和全身细菌感染是 ALI 的主要原因，其中细菌细胞成分起着至关重要的作用。据报道大环内酯/酮内酯抗生素具有免疫调节活性；因此，已经注意到肺炎患者的存活率有所提高。因此，在鼠 LPS 诱导的 ALI 模型中评估了萘霉素（一种新型内酯酮内酯抗菌剂）的免疫调节活性。载体、萘霉素 (100 mg/kg)、阿奇霉素 (600 mg/kg) 和地塞米松 (20 mg/kg) 口服给药，LPS 攻击前 1 小时，然后在 18、24 和 48 小时收集支气管肺泡灌洗液 (BAL) 以确定总细胞计数、总蛋白、髓过氧化物酶 (MPO)、肿瘤坏死因子 (TNF)-α 和白细胞介素 (IL) )-6。目前的研究结果表明，与 LPS 对照组相比，萘霉素预处理显着降低了 BAL 液中的总细胞计数、总蛋白、MPO、TNF-α 和 IL-6 水平。组织病理学评估还表明萘霉素显着减少中性粒细胞浸润。地塞米松，如预期的阳性参考标准，表现出有效的抗炎活性。萘霉素在 100 mg/kg 剂量下的免疫调节作用与阿奇霉素在 600 mg/kg 剂量下的作用相当。由于免疫调节活性，