Roles for early response cytokines during Escherichia coli pneumonia revealed by mice with combined deficiencies of all signaling receptors for TNF and IL-1
Roles for early response cytokines during Escherichia coli pneumonia revealed by mice with combined deficiencies of all signaling receptors for TNF and IL-1
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DOI：
10.1152/ajplung.00353.2003
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发表时间：
2004-06-01
影响因子：
4.9
通讯作者：
Silverman, ES
中科院分区：
文献类型：
--
作者：
Mizgerd, JP;Lupa, MM;Silverman, ES
在感染过程中，炎症对宿主防御是必不可少的，但它会损伤组织并损害器官功能。tnf - α和IL-1 （α和β）是促进炎症的早期反应细胞因子。为了确定这些具有重叠功能的细胞因子的作用，我们培养了三种介导其作用的受体（TNFR1、TNFR2和IL-1RI）均缺失的小鼠。在大肠杆菌肺炎期间，受体缺乏使中性粒细胞募集和水肿积累减少到野生型小鼠的一半。因此，这些受体促成了最大的反应，但实质性的炎症进展独立于它们。受体缺乏损害了某些感染性剂量的抗菌效果。大肠杆菌肺炎期间通气减少不受受体缺乏的影响。然而，肺炎期间肺顺应性的丧失由于受体缺乏而大大减弱。因此，在小鼠大肠杆菌肺炎期间，tnf - α和IL-1信号的缺乏减少了炎症并保持了肺的顺应性。
During infection, inflammation is essential for host defense, but it can injure tissues and compromise organ function. TNF-alpha and IL-1 (alpha and beta) are early response cytokines that facilitate inflammation. To determine the roles of these cytokines with overlapping functions, we generated mice deficient in all of the three receptors mediating their effects (TNFR1, TNFR2, and IL-1RI). During Escherichia coli pneumonia, receptor deficiency decreased neutrophil recruitment and edema accumulation to half of the levels observed in wild-type mice. Thus these receptors contributed to maximal responses, but substantial inflammation progressed independently of them. Receptor deficiency compromised antibacterial efficacy for some infectious doses. Decreased ventilation during E. coli pneumonia was not affected by receptor deficiency. However, the loss of lung compliance during pneumonia was substantially attenuated by receptor deficiency. Thus during E. coli pneumonia in mice, the lack of signaling from TNF-alpha and IL-1 decreases inflammation and preserves lung compliance.