Morphine, but Not Trauma, Sensitizes to Systemic Acinetobacter baumannii Infection
Morphine, but Not Trauma, Sensitizes to Systemic Acinetobacter baumannii Infection
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DOI：
10.1007/s11481-011-9303-6
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发表时间：
2011-12-01
影响因子：
6.2
通讯作者：
Eisenstein, Toby K.
中科院分区：
文献类型：
--
作者：
Breslow, Jessica M.;Monroy, M. Alexandra;Eisenstein, Toby K.
鲍曼不动杆菌是重症监护病房重要的医院感染病原菌。最近，受伤军事人员的发病率有所增加。在许多动物研究中，吗啡被证明具有免疫抑制作用，并对感染敏感。假设进行了测试，吗啡，在战场上用于镇痛，易患不动杆菌感染，阿片类药物可能有一个累加或协同效应与创伤。为了检验这些假设，使用几种不动杆菌属菌株在小鼠中建立腹膜内感染模型。与接受安慰剂颗粒的动物相比，通过植入缓释吗啡颗粒给予吗啡48小时增加死亡率，这种作用被μ阿片受体拮抗剂纳洛酮阻断。吗啡处理小鼠的血液、脾脏、肝脏和肺中的不动杆菌负荷显著高于安慰剂处理动物，证实死亡是由于细菌的增强生长。与安慰剂治疗的小鼠相比，吗啡治疗的小鼠中促炎细胞因子水平也升高。吗啡导致腹腔内细胞总数减少，中性粒细胞百分比和总数减少，巨噬细胞总数减少。吗啡治疗还抑制了嗜中性粒细胞诱导分子IL-17 A和KC/CXCL 1的水平。然而，给予吗啡的IL-17 A（-/-）小鼠对不动杆菌感染的敏感程度并不高于类似治疗的野生型小鼠。单独的创伤对不动杆菌感染不敏感，吗啡和创伤之间没有累加效应。这些结果支持吗啡增强不动杆菌感染的假设。
Acinetobacter baumannii is an important nosocomial pathogen in civilian intensive care units. Recently the incidence has increased in wounded military personnel. Morphine is documented in numerous animal studies to be immunosuppressive and to sensitize to infection. The hypotheses were tested that morphine, administered for analgesia in the battlefield, predisposes to Acinetobacter infection, and that the opioid may have an additive or synergistic effect with trauma. To test these hypotheses, an intraperitoneal infection model was established in mice using several Acinetobacter strains. Morphine administered for 48 h by implantation of a slow-release morphine pellet increased mortality compared to animals receiving a placebo pellet, an effect that was blocked by the mu-opioid receptor antagonist, naltrexone. Acinetobacter burdens in the blood, spleens, livers, and lungs of morphine-treated mice, were significantly higher than those in placebo-treated animals, confirming that mortality was due to potentiated growth of the bacteria. There were also elevated levels of pro-inflammatory cytokines in morphine-treated versus placebo-treated mice. Morphine caused a reduction in the total number of cells in the peritoneal cavity, a decrease in the percentage and total numbers of neutrophils, and a decrease in the total number of macrophages. Morphine treatment also suppressed levels of the neutrophil-inducing molecules, IL-17A and KC/CXCL1. However, IL-17A(-/-) mice given morphine were not sensitized to Acintobacter infection to a greater degree than similarly treated wild-type mice. Trauma alone did not sensitize to Acinetobacter infection, and there was no additive effect between morphine and trauma. These results support the hypothesis that morphine potentiates Acinetobacter infection.