Tsao Nina, Kuo Chih-Feng, Chiu Ching-Chen, Lin Wei-Chen, Huang Wan-Hui, Chen Li-Yang
Department of Biological Science and Technology, I-Shou University, Kaohsiung City, Taiwan
Department of Nursing, I-Shou University, Kaohsiung City, Taiwan.
Antimicrob Agents Chemother. 2015 Mar;59(3):1525-33. doi: 10.1128/AAC.04261-14. Epub 2014 Dec 22.
Intragastric Klebsiella pneumoniae infections of mice can cause liver abscesses, necrosis of liver tissues, and bacteremia. Lithium chloride, a widely prescribed drug for bipolar mood disorder, has been reported to possess anti-inflammatory properties. Using an intragastric infection model, the effects of LiCl on K. pneumoniae infections were examined. Providing mice with drinking water containing LiCl immediately after infection protected them from K. pneumoniae-induced death and liver injuries, such as necrosis of liver tissues, as well as increasing blood levels of aspartate aminotransferase and alanine aminotransferase, in a dose-dependent manner. LiCl administered as late as 24 h postinfection still provided protection. Monitoring of the LiCl concentrations in the sera of K. pneumoniae-infected mice showed that approximately 0.33 mM LiCl was the most effective dose for protecting mice against infections, which is lower than the clinically toxic dose of LiCl. Surveys of bacterial counts and cytokine expression levels in LiCl-treated mice revealed that both were effectively inhibited in blood and liver tissues. Using in vitro assays, we found that LiCl (5 μM to 1 mM) did not directly interfere with the growth of K. pneumoniae but made K. pneumoniae cells lose the mucoid phenotype and become more susceptible to macrophage killing. Furthermore, low doses of LiCl also partially enhanced the bactericidal activity of macrophages. Taken together, these data suggest that LiCl is an alternative therapeutic agent for K. pneumoniae-induced liver infections.
小鼠胃内感染肺炎克雷伯菌可导致肝脓肿、肝组织坏死和菌血症。氯化锂是一种广泛用于治疗双相情感障碍的药物，据报道具有抗炎特性。利用胃内感染模型，研究了氯化锂对肺炎克雷伯菌感染的影响。感染后立即给小鼠提供含氯化锂的饮用水，可使它们免受肺炎克雷伯菌诱导的死亡和肝损伤，如肝组织坏死，以及以剂量依赖方式升高血清天冬氨酸转氨酶和丙氨酸转氨酶水平。感染后24小时给予氯化锂仍能提供保护。对肺炎克雷伯菌感染小鼠血清中氯化锂浓度的监测表明，约0.33 mM氯化锂是保护小鼠免受感染的最有效剂量，该剂量低于氯化锂的临床中毒剂量。对氯化锂处理小鼠的细菌计数和细胞因子表达水平的调查显示，血液和肝组织中的这两者均受到有效抑制。通过体外试验，我们发现氯化锂（5 μM至1 mM）不会直接干扰肺炎克雷伯菌的生长，但会使肺炎克雷伯菌细胞失去黏液样表型，变得更易被巨噬细胞杀灭。此外，低剂量的氯化锂还部分增强了巨噬细胞的杀菌活性。综上所述，这些数据表明氯化锂是治疗肺炎克雷伯菌诱导的肝脏感染的一种替代治疗药物。
