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脓毒症和非脓毒症患者胸腔积液中的细胞因子及可溶性细胞因子受体

Cytokines and soluble cytokine receptors in pleural effusions from septic and nonseptic patients.

作者信息

Marie C, Losser M R, Fitting C, Kermarrec N, Payen D, Cavaillon J M

机构信息

Unité d'Immuno-Allergie, Institut Pasteur, Paris, France.

出版信息

Am J Respir Crit Care Med. 1997 Nov;156(5):1515-22. doi: 10.1164/ajrccm.156.5.9702108.

Abstract

The balance between proinflammatory cytokines and their inhibitors has rarely been investigated in pleural effusions of nonmalignant or noninfectious origin. To evaluate the impact of a lung and/or intrathoracic infection in such a circumstance, we compared the levels of proinflammatory cytokines (interleukin-8 [IL-8]); tumor necrosis factor-alpha (TNF-alpha); the cytokine antagonists and inhibitors (IL-1 receptor antagonist [IL-1ra]) and soluble TNF receptors Types I and II (sTNFRI, sTNFRII); and antiinflammatory cytokines (transforming growth factor-beta [TGF-beta]) in pleural effusion and plasma from septic (n = 15) and nonseptic (n = 9) patients. In addition, we analyzed the levels of IL-6 and its soluble receptor (sIL-6R). Bronchoalveolar lavage fluids (BALFs) were also studied in a few septic patients. High and nonsignificantly different levels of cytokines and inhibitors were detected in both groups of patients. The levels of IL-6 and sTNFRI and sTNFRII in pleural effusion were higher than in plasma, whereas the levels of IL-1ra and sIL-6R were higher in plasma. The levels of sIL-6R influenced the bioactivity of IL-6. There was no correlation between the levels of cytokines in plasma and in pleural effusion. In contrast, a significant correlation was observed for the soluble receptors sIL-6R (r = 0.67, p < 0.001), sTNFRI (r = 0.76, p < 0.001) and sTNFRII (r = 0.66, p = 0.001). Furthermore, a high correlation was found between the levels of both forms of sTNFRs in plasma (r = 0.95, p < 0.001) and in pleural effusion (r = 0.79, p < 0.001). In addition, a correlation was observed between the levels of TGF-beta in pleural effusion and in BALF. The highest levels of some markers in plasma and of others in pleura argue in favor of both a systemic and a compartmentalized response, independently of the presence of infection. Because cytokines can be trapped by the surrounding cells in their environment, measurable levels of cytokines in biologic fluids represent the "tip of the iceberg," which is not the case for soluble receptors. The correlations of these latter markers between plasma and pleura strongly suggest that exchanges between both compartments can occur in both directions.

摘要

促炎细胞因子与其抑制剂之间的平衡在非恶性或非感染性胸腔积液中鲜有研究。为评估肺部和/或胸腔内感染在此种情况下的影响,我们比较了脓毒症患者(n = 15)和非脓毒症患者(n = 9)胸腔积液和血浆中促炎细胞因子(白细胞介素-8 [IL-8]、肿瘤坏死因子-α [TNF-α])、细胞因子拮抗剂和抑制剂(IL-1受体拮抗剂[IL-1ra])以及I型和II型可溶性TNF受体(sTNFRI、sTNFRII)和抗炎细胞因子(转化生长因子-β [TGF-β])的水平。此外,我们分析了IL-6及其可溶性受体(sIL-6R)的水平。还对少数脓毒症患者的支气管肺泡灌洗液(BALF)进行了研究。两组患者中细胞因子和抑制剂的水平均较高,但差异无统计学意义。胸腔积液中IL-6、sTNFRI和sTNFRII的水平高于血浆,而血浆中IL-1ra和sIL-6R的水平较高。sIL-6R的水平影响IL-6的生物活性。血浆和胸腔积液中细胞因子的水平之间无相关性。相反,可溶性受体sIL-6R(r = 0.67,p < 0.001)、sTNFRI(r = 0.76,p < 0.001)和sTNFRII(r = 0.66,p = 0.001)之间存在显著相关性。此外,血浆和胸腔积液中两种形式的sTNFRs水平之间存在高度相关性(r = 0.95,p < 0.001)和(r = 0.79,p < 0.001)。此外,胸腔积液和BALF中TGF-β的水平之间存在相关性。血浆中某些标志物水平最高,而胸膜中其他标志物水平最高,这表明无论是否存在感染,都存在全身和局部反应。由于细胞因子可被其周围环境中的细胞捕获,生物体液中可测量的细胞因子水平仅代表“冰山一角”,而可溶性受体则并非如此。这些后一种标志物在血浆和胸膜之间的相关性强烈表明,两个腔室之间可以双向进行交换。

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