Lung inflammatory responses to intratracheal interleukin-1α in ventilated preterm lambs
Lung inflammatory responses to intratracheal interleukin-1α in ventilated preterm lambs
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DOI：
10.1203/01.pdr.0000112104.48903.3c
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发表时间：
2004-04-01
影响因子：
3.6
通讯作者：
Ikegami, M
中科院分区：
文献类型：
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作者：
Mulrooney, N;Jobe, AH;Ikegami, M
白细胞介素-1 α是一种早期反应的促炎细胞因子，与绒毛膜炎、早产、脑损伤和支气管肺发育不良有关。然而，IL-1 α也可以增加表面活性蛋白的表达，并诱导早产儿肺成熟。我们测量了IL-1 α的影响，通过肠道滴注（IT），并比较了与静脉注射IL-1 α在表面处理和通气的早产羔羊的反应。IT重组羊IL-1 α在5和50 μ g/kg剂量下引起类似的大量中性粒细胞募集到支气管肺泡灌洗液中。中性粒细胞表达CD 11b、CD 14和CD 44，但不产生增加量的H2 O2。来自支气管肺泡灌洗液的细胞具有促炎细胞因子的表达增加，其在来自肺组织的mRNA中也增加。IT IL-1 α还抑制表面活性蛋白-C mRNA的表达。全身效应为50 μ g/kg IL-1 α IT组中血液中中性粒细胞减少、肺功能降低、心率增加和低血压或死亡，而5 μ g/kg IL-1 α IT组中仅血液中中性粒细胞减少。i. v. IL-1 α未引起肺部炎症或损伤，但确实导致重度中性粒细胞减少症和低血压，导致早期死亡。IT IL-1 α可导致严重的肺部炎症和通气早产儿肺的全身性休克。
Interleukin-1alpha is an early response proinflammatory cytokine that has been associated with chorioamnionitis and preterm labor, brain injury, and bronchopulmonary dysplasia. However, IL-1alpha also can increase expression of surfactant proteins and induce lung maturation in the preterm fetus. We measured the effects of IL-1alpha given by intratracheal instillation (IT) and compared the responses with injection of i.v. IL-1alpha in surfactant-treated and ventilated premature lambs. IT recombinant ovine IL-1alpha at doses of 5 and 50 mug/kg caused a similar large recruitment of neutrophils into the bronchoalveolar lavage fluid. The neutrophils expressed CD11b, CD14, and CD44, but did not produce increased amounts of H2O2. Cells from the bronchoalveolar lavage fluid had increased expression of proinflammatory cytokines, which also were increased in mRNA from lung tissue. The IT IL-1alpha also suppressed the expression of surfactant protein-C mRNA. Systemic effects were decreased neutrophils in blood, decreased lung function, increased heart rate, and hypotension or death in the 50 mug/kg IL-1alpha IT group and only decreased neutrophils in the blood in the 5 mug/kg IL-1alpha IT group. The i.v. IL-1alpha caused no lung inflammation or injury but did result in severe neutropenia and hypotension leading to early death. IT IL-1alpha can cause intense lung inflammation and systemic shock in ventilated preterm lungs.