Agonists of peroxisome proliferator-activated receptor (PPAR)-γ have been suggested as potential adjuvant therapy in bacterial pneumonia because of their capacity to inhibit inflammation and enhance bacterial clearance. Previous studies only assessed the effects of pretreatment with these compounds, thereby bearing less relevance for the clinical scenario. Moreover, PPAR-γ agonists have not been studied in pneumonia caused by Klebsiella pneumoniae, a common human respiratory pathogen of which antibiotic treatment is hampered by increasing antimicrobial resistance. Here we show that administration of the PPAR-γ agonist pioglitazone 6 or 8 h after infection of mice with a highly virulent strain of Klebsiella pneumoniae via the airways results in reduced cytokine and myeloperoxidase levels in the lungs at 24 h after infection, as well as reduced bacterial growth in the lungs and decreased dissemination to distant organs at 42 h post-infection. These results suggest that pioglitazone may be an interesting agent in the treatment of Klebsiella pneumonia.

中文翻译：

---

用 PPAR-γ 激动剂吡格列酮后处理抑制肺炎克雷伯菌期间的炎症和细菌生长

过氧化物酶体增殖物激活受体 (PPAR)-γ 的激动剂已被建议作为细菌性肺炎的潜在辅助治疗，因为它们具有抑制炎症和增强细菌清除的能力。以前的研究仅评估了用这些化合物进行预处理的效果，因此与临床情况的相关性较小。此外，尚未在由肺炎克雷伯菌引起的肺炎中研究 PPAR-γ 激动剂，这是一种常见的人类呼吸道病原体，其抗生素治疗因抗菌素耐药性增加而受到阻碍。在这里，我们显示通过气道感染高毒力肺炎克雷伯菌菌株的小鼠 6 或 8 小时施用 PPAR-γ 激动剂吡格列酮导致感染后 24 小时肺中细胞因子和髓过氧化物酶水平降低，以及在感染后 42 小时减少肺部细菌生长并减少向远处器官的传播。这些结果表明，吡格列酮可能是治疗肺炎克雷伯菌的有趣药物。