TNF-α Compensates for the Impaired Host Defense of IL-1 Type I Receptor-Deficient Mice During Pneumococcal Pneumonia1

TNF-α Compensates for the Impaired Host Defense of IL-1 Type I Receptor-Deficient Mice During Pneumococcal Pneumonia1
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TNF-α 可补偿肺炎球菌肺炎期间 IL-1 I 型受体缺陷小鼠受损的宿主防御1

DOI:
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发表时间:
2001
影响因子:
4.4
通讯作者:
T. van der Poll
T. van der Poll
中科院分区:
医学2区
文献类型:
--
作者:
A. Rijneveld;S. Florquin;J. Branger;P. Speelman;S. V. van Deventer;T. van der Poll

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为探讨IL-1在肺炎宿主防御中的作用,将IL-1R I型缺陷(IL-1R−/−)小鼠和野生型(Wt)小鼠鼻内接种肺炎链球菌。肺炎导致肺组织中IL-1α和IL-1β基因和蛋白水平升高。IL-1R−/−和Wt小鼠接种5×104CFU和2×105CFU后的存活率无明显差异。在早期时间点(24小时和48小时),IL-1R−/−小鼠的肺部肺炎链球菌菌落数比Wt小鼠多2个对数;72小时时,两组小鼠肺内细菌的生长情况相似。组织病理学检查显示,IL-1R−/−小鼠在肺炎诱导后24小时形成炎症细胞的能力降低。IL-1R−/−小鼠在接种后24 h肺泡灌洗液中粒细胞内流也明显减少。由于已知肿瘤坏死因子可以增强肺炎期间的宿主防御,我们确定了内源性肿瘤坏死因子在IL-1R−/−小鼠早期防御机制受损和随后恢复中的作用。IL-1R−/−组小鼠4天后全部死亡(14只小鼠无存活),而IL-1R−/−小鼠(对照抗体)、Wt小鼠(抗肿瘤坏死因子抗体)和Wt小鼠(对照抗体)10天存活率分别为7/13、3/14和12/13。这些数据表明,在肺炎球菌肺炎的宿主防御中,肿瘤坏死因子比IL-1更重要,IL-1R−/−小鼠早期受损的宿主防御在后期被肿瘤坏死因子补偿。
To determine the role of IL-1 in the host defense against pneumonia, IL-1R type I-deficient (IL-1R−/−) and wild-type (Wt) mice were intranasally inoculated with Streptococcus pneumoniae. Pneumonia resulted in elevated IL-1α and IL-1β mRNA and protein levels in the lungs. Survival rates did not differ between IL-1R−/− and Wt mice after inoculation with 5 × 104 or 2 × 105 CFU. At early time points (24 and 48 h) IL-1R−/− mice had 2-log more S. pneumoniae CFU in lungs than Wt mice; at 72 h bacterial outgrowth in lungs was similar in both groups. Upon histopathologic examination IL-1R−/− mice displayed a reduced capacity to form inflammatory infiltrates at 24 h after the induction of pneumonia. IL-1R−/− mice also had significantly less granulocyte influx in bronchoalveolar lavage fluid at 24 h after inoculation. Since TNF is known to enhance host defense during pneumonia, we determined the role of endogenous TNF in the early impairment and subsequent recovery of defense mechanisms in IL-1R−/− mice. All IL-1R−/− mice treated with anti-TNF rapidly died (no survivors (of 14 mice) after 4 days), while 10-day survival in IL-1R−/− mice (control Ab), Wt mice (anti-TNF), and Wt mice (control Ab) was 7 of 13, 3 of 14, and 12 of 13, respectively. These data suggest that TNF is more important for host defense against pneumococcal pneumonia than IL-1, and that the impaired early host defense in IL-1R−/− mice is compensated for by TNF at a later phase.
DOI: --
发表时间: 1991
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影响因子: --
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发表时间: 1990-01-01
影响因子: 6.4
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患有细菌性肺部感染的儿童的支气管肺泡洗液中白细胞介素 1 的水平升高。
DOI: 10.1164/ajrccm/142.2.365
发表时间: 1990
期刊: The American review of respiratory disease
影响因子: --
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