Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of Mycoplasma pneumoniae Pneumonia
Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of Mycoplasma pneumoniae Pneumonia
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DOI：
10.1128/aac.00979-08
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发表时间：
2009-04-01
影响因子：
4.9
通讯作者：
Hardy, R. D.
中科院分区：
文献类型：
--
作者：
Salvatore, C. M.;Techasaensiri, C.;Hardy, R. D.
肺炎支原体是引起非典型社区获得性肺炎的病原体之一。替加环素属于一类新的甘环素抗菌剂，对多种微生物具有活性，包括体外对肺炎支原体的活性。我们研究了替加环素对肺炎支原体肺炎小鼠模型的微生物学、组织学和免疫学指标的影响。BALB/c小鼠鼻内接种肺炎支原体，皮下给予替加环素或安慰剂治疗6天。结果变量包括定量支气管肺泡灌洗（BAL）肺炎支原体培养、肺组织病理学评分（HPS）、BAL细胞因子和趋化因子浓度（肿瘤坏死因子α [tnf - α]、γ干扰素[ifn - γ]、白细胞介素1 β [IL-1 β]、IL-2、IL-4、IL-5、IL-6、IL-10、IL-12 [p40/p70]、粒细胞-巨噬细胞集落刺激因子、MIP-1 α、MIG、KC、MCP-1和IP-10）。替加环素（MpTige）治疗小鼠的BAL肺炎支原体浓度与安慰剂（MpPl）治疗小鼠相比有降低的趋势；然而，这并没有达到统计学意义。与MpPl小鼠相比，MpTige小鼠的肺HPS和实质肺炎亚评分明显较低。MpTige小鼠BAL细胞因子IL-1 β、IL-12 （p40/p70）、ifn - γ和tnf - α浓度显著降低；趋化因子MIG、MIP-1 α和IP-10在MpTige小鼠中的含量均有统计学意义降低。虽然替加环素治疗显示出适度的微生物作用，但它显著改善了肺组织学炎症，减少了肺细胞因子和趋化因子。
Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against M. pneumoniae. We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of M. pneumoniae pneumonia. BALB/c mice were inoculated intranasally with M. pneumoniae and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], interleukin 1 beta [IL-1 beta], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1 alpha, MIG, KC, MCP-1, and IP-10). BAL M. pneumoniae concentrations in mice treated with tigecycline (MpTige) tended to be reduced compared with mice treated with placebo (MpPl); however this did not reach statistical significance. The lung HPS was significantly lower, as well as the parenchymal-pneumonia subscore, in the MpTige mice than in the MpPl mice. MpTige mice had significantly lower BAL cytokine concentrations of IL-1 beta, IL-12 (p40/p70), IFN-gamma, and TNF-alpha; of the chemokines, MIG, MIP-1 alpha, and IP-10 were statistically lower in MpTige mice. While tigecycline treatment demonstrated a modest microbiologic effect, it significantly improved lung histologic inflammation and reduced pulmonary cytokines and chemokines.