Phage Therapy of Pneumonia Is Not Associated with an Overstimulation of the Inflammatory Response Compared to Antibiotic Treatment in Mice
Phage Therapy of Pneumonia Is Not Associated with an Overstimulation of the Inflammatory Response Compared to Antibiotic Treatment in Mice
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DOI：
10.1128/aac.00379-19
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发表时间：
2019-08-01
影响因子：
4.9
通讯作者：
Debarbieux, Laurent
中科院分区：
文献类型：
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作者：
Dufour, Nicolas;Delattre, Raphaelle;Debarbieux, Laurent
在一些国家多年的临床使用和最近的实验模型文献的支持下，以及在欧洲和美国的同情使用，噬菌体治疗正在为难以治疗的细菌感染提供解决方案。然而，关于这些处理对宿主影响的研究仍然很少。用两种特异性噬菌体（536_P1和LM33_P1；鼻内）或抗生素（头孢曲松、头孢西丁或亚胺培南-西司他汀；腹腔）治疗由两种致病性大肠杆菌菌株（536和LM33）引起的小鼠急性肺炎。健康小鼠也单独接受了噬菌体。在早期（-20 h）时间点检测肺水肿严重程度、急性炎症细胞因子浓度（血液和肺匀浆）、全血计数、细菌和噬菌体计数。噬菌体降低细菌负荷的效果比抗生素更快，但两者的终点相似。噬菌体治疗与过度炎症无关，相反，与抗生素相比，噬菌体治疗倾向于降低炎症，并能更快地纠正血细胞计数异常。在没有细菌感染的情况下，噬菌体536_P1促进肺部抗病毒细胞因子（γ干扰素[ifn - γ]和白细胞介素-12 [IL-12]）和趋化因子的产生微弱增加，但在血液中没有。然而，当使用噬菌体536_P1治疗受感染的动物时，不再观察到这种变异。与抗生素治疗相比，噬菌体在体内快速裂解细菌并不会增加先天炎症反应。
Supported by years of clinical use in some countries and more recently by literature on experimental models, as well as its compassionate use in Europe and in the United States, bacteriophage (phage) therapy is providing a solution for difficult-to-treat bacterial infections. However, studies of the impact of such treatments on the host remain scarce. Murine acute pneumonia initiated by intranasal instillation of two pathogenic strains of Escherichia coli (536 and LM33) was treated by two specific bacteriophages (536_P1 and LM33_P1; intranasal) or antibiotics (ceftriaxone, cefoxitin, or imipenem-cilastatin; intraperitoneal). Healthy mice also received phages alone. The severity of pulmonary edema, acute inflammatory cytokine concentration (blood and lung homogenates), complete blood counts, and bacterial and bacteriophage counts were determined at early (-20 h) time points. The efficacy of bacteriophage to decrease bacterial load was faster than with antibiotics, but the two displayed similar endpoints. Bacteriophage treatment was not associated with overinflammation but in contrast tended to lower inflammation and provided a faster correction of blood cell count abnormalities than did antibiotics. In the absence of bacterial infection, bacteriophage 536_P1 promoted a weak increase in the production of antiviral cytokines (gamma interferon [IFN-gamma] and interleukin-12 [IL-12]) and chemokines in the lungs but not in the blood. However, such variations were no longer observed when bacteriophage 536_P1 was administered to treat infected animals. The rapid lysis of bacteria by bacteriophages in vivo does not increase the innate inflammatory response compared to that with antibiotic treatment.