Cytokine balance in the lungs of patients with acute respiratory distress syndrome

Cytokine balance in the lungs of patients with acute respiratory distress syndrome
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DOI:
10.1164/ajrccm.164.10.2104013
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发表时间:
2001-11-15
影响因子:
24.7
通讯作者:
Martin, TR
Martin, TR
中科院分区:
医学1区
文献类型:
--
作者:
Park, WY;Goodman, RB;Martin, TR

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急性呼吸窘迫综合征(ARDS)涉及肺部强烈的炎症反应,伴支气管肺泡灌洗液(BALF)中促炎和抗炎细胞因子的积累。我们的目的是确定在ARDS发病前后肺部促炎介质和抗炎介质之间的平衡是如何变化的。我们确定了23例有ARDS风险的患者和46例已确诊的ARDS患者,并进行了一系列支气管肺泡灌洗(BAL)。我们使用免疫分析法测量肿瘤坏死因子α (tnf - α)和可溶性tnf - α受体I和II;白细胞介素1 β (IL-1 β), IL-1 β受体拮抗剂和可溶性IL-1受体II;IL-6及可溶性IL-6受体;和il - 10。我们使用灵敏的生物测定法来测量净tnf - α、IL-1 β和IL-6活性。虽然个体细胞因子在ARDS发病前后增加,但同源受体和/或拮抗剂的增加更大,因此在ARDS发病时激动剂/拮抗剂的摩尔比急剧下降。摩尔比保持低7天或更长时间,限制了急性呼吸窘迫综合征发病时肺中可溶性IL-1 β和tnf - α的活性。ARDS早期这种显著的抗炎反应可能是限制肺部净炎症反应的关键机制。
Acute respiratory distress syndrome (ARDS) involves an Intense Inflammatory response in the lungs, with accumulation of both pro- and antiinflammatory cytokines in bronchoalveolar lavage fluid (BALF). Our goal was to determine how the balance between pro- and antiinflammatory mediators in the lungs changes before and after the onset of ARDS. We identified 23 patients at risk for ARDS and 46 with established ARDS and performed serial bronchoalveolar lavage (BAL). We used immunoassays to measure tumor necrosis factor alpha (TNF-alpha) and soluble TNF-alpha receptors I and II; interleukin 1 beta (IL-1 beta), IL-1 beta receptor antagonist, and soluble IL-1 receptor II; IL-6 and soluble IL-6 receptor; and IL-10. We used sensitive bioassays to measure net TNF-alpha, IL-1 beta and IL-6 activity. Although individual cytokines increased before and after onset of ARDS, greater increases occurred in cognate receptors and/or antagonists, so that molar ratios of agonists/antagonists declined dramatically at the onset of ARDS. The molar ratios remained low for 7 d or longer, limiting the activity of soluble IL-1 beta and TNF-alpha in the lungs at the onset of ARDS. This significant antiinflammatory response early in ARDS may provide a key mechanism for limiting the net inflammatory response in the lungs.