Potentiating effect of morphine on oral Salmonella enterica serovar Typhimurium infection is μ-opioid receptor-dependent
Potentiating effect of morphine on oral Salmonella enterica serovar Typhimurium infection is μ-opioid receptor-dependent
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DOI：
10.1016/j.micpath.2010.07.006
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发表时间：
2010-12-01
影响因子：
3.8
通讯作者：
Eisenstein, Toby K.
中科院分区：
文献类型：
--
作者：
Breslow, Jessica M.;Feng, Pu;Eisenstein, Toby K.
我们实验室以前的研究表明，用吗啡丸处理的小鼠对沙门氏菌、鼠伤寒血清型感染敏感。然而，阿片受体拮抗剂纳洛酮只能部分阻断吗啡的作用，这增加了阿片类药物通过非阿片受体发挥作用的可能性。为了进一步阐明对感染的致敏是否是阿片受体依赖性现象，在本研究中使用μ-阿片受体敲除（MORKO）小鼠。用吗啡处理野生型（WT）和MORKO小鼠，并通过死亡率、肠道相关淋巴组织和血液和腹膜液中的细菌负荷以及血浆中促炎细胞因子的水平来评估它们对口服沙门氏菌感染的敏感性。用吗啡处理的MORKO动物对亚致死剂量的沙门氏菌是难治的，而WT动物的类似处理导致100%的死亡率。用吗啡处理的WT动物在所有测试的器官中具有高细菌负荷，而吗啡处理的MORKO动物在任何器官中都没有可培养的沙门氏菌。促炎细胞因子水平升高，吗啡治疗的WT，但不是MORKO小鼠感染沙门氏菌。这些结果提供了明确的证据表明，吗啡介导的口腔沙门氏菌感染的增强依赖于μ阿片受体。(C)2010爱思唯尔有限公司版权所有。
Previous studies from our laboratory demonstrated that mice treated with morphine pellets are sensitized to Salmonella enterica, serovar Typhimurium infection. However, the opioid receptor antagonist, naltrexone, only partially blocked the effect of morphine, raising the possibility that the opioid might have some of its effects through a nonopioid receptor. To further clarify whether sensitization to infection is an opioid receptor-dependent phenomenon, mu-opioid receptor knockout (MORKO) mice were used in the present study. Wild-type (WT) and MORKO mice were treated with morphine and their sensitivity to oral Salmonella infection was assessed by mortality, bacterial burdens in gut associated lymphoid tissue and in blood and peritoneal fluid, and by levels of pro-inflammatory cytokines in plasma. MORKO animals treated with morphine were refractory to a sublethal dose of Salmonella, while similar treatment of WT animals resulted in 100% mortality. WT animals treated with morphine had high bacterial loads in all organs tested, while morphine-treated MORKO animals had no culturable Salmonella in any organs. Pro-inflammatory cytokine levels were elevated in morphine-treated WT but not MORKO mice infected with Salmonella. These results provide definitive evidence that the morphine-mediated enhancement of oral Salmonella infection is dependent on the mu-opioid receptor. (C) 2010 Elsevier Ltd. All rights reserved.