Patel Anasuya M, Periasamy Hariharan, Mokale Santosh N
Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Marg, Aurangabad, Maharashtra, India.
Wockhardt Research Centre, Aurangabad, Maharashtra, India.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Sep;393(9):1671-1679. doi: 10.1007/s00210-020-01876-4. Epub 2020 May 7.
Sepsis is a life-threatening organ dysfunction resulting from inflammatory responses instigated by toxins secreted by bacteria. Immunomodulatory effect of clindamycin is earlier reported in a murine lipopolysaccharide (LPS)-induced sepsis model. There are no studies demonstrating the immunomodulatory effect of clindamycin in combination with ceftriaxone in a clinically relevant murine polymicrobial sepsis model induced by cecal ligation and puncture (CLP). Ceftriaxone is combined to control the bacterial growth. Following 3 h of CLP challenge, Swiss albino mice were administered vehicle, ceftriaxone alone (100 mg/kg, subcutaneously), and in combination with clindamycin at immunomodulatory dose (200 mg/kg, intraperitoneally). Survival was assessed for 5 days, and bacterial count and biochemical and physiological parameters were measured after 18 h of CLP challenge. Ceftriaxone alone caused significant reduction in bacterial count in blood, peritoneal fluid, lung, liver, and kidney homogenate which was not further substantially reduced by ceftriaxone and clindamycin combination. Day 5 survival was greatly improved by combination compared with ceftriaxone alone which was also evident through marked drop in blood glucose, total white blood cell (WBC) count, and body temperature. The combination group significantly mitigated the cytokine (tumor necrosis factor (TNF)-α and interleukin (IL)-6) and myeloperoxidase (MPO) levels in plasma, lung, liver, and kidney of CLP-challenged mice, which further helped in significantly suppressing the elevated levels of liver and kidney function parameters. Clindamycin at immunomodulatory dose in combination with ceftriaxone attenuated organ damage and improved survival of septic mice by suppressing infection, inflammatory responses, and oxidative stress.
脓毒症是一种由细菌分泌的毒素引发的炎症反应导致的危及生命的器官功能障碍。克林霉素的免疫调节作用在小鼠脂多糖（LPS）诱导的脓毒症模型中已有较早报道。尚无研究证明在盲肠结扎穿刺（CLP）诱导的具有临床相关性的小鼠多微生物脓毒症模型中，克林霉素与头孢曲松联合使用的免疫调节作用。联合使用头孢曲松以控制细菌生长。在CLP攻击3小时后，给瑞士白化小鼠分别注射赋形剂、单独的头孢曲松（100mg/kg，皮下注射）以及与免疫调节剂量的克林霉素（200mg/kg，腹腔注射）联合使用。评估5天的存活率，并在CLP攻击18小时后测量细菌计数以及生化和生理参数。单独使用头孢曲松可使血液、腹腔液、肺、肝和肾匀浆中的细菌计数显著降低，而头孢曲松与克林霉素联合使用并未使其进一步大幅降低。与单独使用头孢曲松相比，联合使用可使第5天的存活率大大提高，这也通过血糖、总白细胞（WBC）计数和体温的显著下降得以体现。联合使用组显著减轻了CLP攻击小鼠血浆、肺、肝和肾中的细胞因子（肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6）以及髓过氧化物酶（MPO）水平，这进一步有助于显著抑制肝肾功能参数的升高。免疫调节剂量的克林霉素与头孢曲松联合使用可通过抑制感染、炎症反应和氧化应激来减轻器官损伤并提高脓毒症小鼠的存活率。
