Ciprofloxacin modulates cytokine/chemokine profile in serum, improves bone marrow repopulation, and limits apoptosis and autophagy in ileum after whole body ionizing irradiation combined with skin-wound trauma.
Ciprofloxacin modulates cytokine/chemokine profile in serum, improves bone marrow repopulation, and limits apoptosis and autophagy in ileum after whole body ionizing irradiation combined with skin-wound trauma.
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DOI：
10.1371/journal.pone.0058389
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kiang JG
中科院分区：
文献类型：
--
作者：
Fukumoto R;Cary LH;Gorbunov NV;Lombardini ED;Elliott TB;Kiang JG
放射复合伤（radiation combined injury，CI）是指放射性损伤（radiation injury，RI）与其他类型损伤的复合，其死亡率通常高于单纯RI。一系列特定的、时间依赖性的病理生理变化与CI相关。在这些变化中，促炎细胞因子的大量释放、严重的造血和胃肠道损失以及细菌性脓毒症是改善存活率的重要治疗靶点。环丙沙星（CIP）除具有抗菌活性外，还具有免疫调节作用。本研究报告说，CIP改善了CI特有的病理生理变化，这些变化后来导致了重大死亡。B6 D2 F1/J小鼠在第0天通过RI接着伤口创伤接受CI，并用CIP（90 mg/kg p.o.，q.d. CI后2小时内至第10天）。在第10天，CIP处理不仅显著降低促炎细胞因子和趋化因子浓度，包括白细胞介素-6（IL-6）和KC（即，IL-8），但与载体处理的对照相比，它也增强了IL-3的产生。用CIP处理的小鼠显示出更大的骨髓细胞再增殖。CIP还限制了CI诱导的回肠绒毛细胞凋亡和自噬、全身性细菌感染和伊加产生。CI后，CIP治疗导致LD 0/10，而溶媒治疗组为LD 20/10。鉴于CIP在我们的实验中显示的多种有益活性，CIP可能被证明是一种有用的CI治疗药物。
Radiation combined injury (CI) is a radiation injury (RI) combined with other types of injury, which generally leads to greater mortality than RI alone. A spectrum of specific, time-dependent pathophysiological changes is associated with CI. Of these changes, the massive release of pro-inflammatory cytokines, severe hematopoietic and gastrointestinal losses and bacterial sepsis are important treatment targets to improve survival. Ciprofloxacin (CIP) is known to have immunomodulatory effect besides the antimicrobial activity. The present study reports that CIP ameliorated pathophysiological changes unique to CI that later led to major mortality. B6D2F1/J mice received CI on day 0, by RI followed by wound trauma, and were treated with CIP (90 mg/kg p.o., q.d. within 2 h after CI through day 10). At day 10, CIP treatment not only significantly reduced pro-inflammatory cytokine and chemokine concentrations, including interleukin-6 (IL-6) and KC (i.e., IL-8 in human), but it also enhanced IL-3 production compared to vehicle-treated controls. Mice treated with CIP displayed a greater repopulation of bone marrow cells. CIP also limited CI-induced apoptosis and autophagy in ileal villi, systemic bacterial infection, and IgA production. CIP treatment led to LD0/10 compared to LD20/10 for vehicle-treated group after CI. Given the multiple beneficial activities of CIP shown in our experiments, CIP may prove to be a useful therapeutic drug for CI.