Adjunctive Corticosteroid Therapy Improves Lung Immunopathology and Survival During Severe Secondary Pneumococcal Pneumonia in Mice
Adjunctive Corticosteroid Therapy Improves Lung Immunopathology and Survival During Severe Secondary Pneumococcal Pneumonia in Mice
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DOI：
10.1093/infdis/jit653
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发表时间：
2014-05-01
影响因子：
6.4
通讯作者：
McCullers, Jonathan A.
中科院分区：
文献类型：
--
作者：
Ghoneim, Hazem E.;McCullers, Jonathan A.
继发性细菌性肺炎是流感期间发病和死亡的重要原因，尽管常规使用标准抗生素。抗生素诱导的与细菌细胞壁裂解相关的免疫病理已被认为是导致这些不良结果的原因。在流感后继发性细菌性肺炎（SBP）的小鼠模型中使用肺炎链球菌，我们通过体内生物发光成像根据肺部的肺炎球菌负荷对疾病严重程度进行分层。氨苄西林治疗治愈了轻度肺炎小鼠，但对严重肺炎小鼠无效，尽管有效地杀死了细菌。辅助地塞米松治疗改善了氨苄西林诱导的免疫病理，改善了严重收缩压小鼠的预后。然而，在原发性流感感染期间，早期地塞米松治疗会损害肺适应性免疫，表现为病毒滴度增加，并伴随其在收缩压中的保护功能丧失。这些数据支持在严重的社区获得性肺炎病例中辅助使用皮质类固醇。
Secondary bacterial pneumonia is a significant cause of morbidity and mortality during influenza, despite routine use of standard antibiotics. Antibiotic-induced immunopathology associated with bacterial cell wall lysis has been suggested to contribute to these poor outcomes. Using Streptococcus pneumoniae in a well-established murine model of secondary bacterial pneumonia (SBP) following influenza, we stratified disease severity based on pneumococcal load in the lungs via in vivo bioluminescence imaging. Ampicillin treatment cured mice with mild pneumonia but was ineffective against severely pneumonic mice, despite effective bacterial killing. Adjunctive dexamethasone therapy improved ampicillin-induced immunopathology and improved outcomes in mice with severe SBP. However, early dexamethasone therapy during primary influenza infection impaired lung adaptive immunity as manifest by increased viral titers, with an associated loss of its protective functions in SBP. These data support adjunctive clinical use of corticosteroids in severe cases of community-acquired pneumonia.