Elevated CXCL10 (IP-10) in bronchoalveolar lavage fluid is associated with acute cellular rejection after human lung transplantation.
Elevated CXCL10 (IP-10) in bronchoalveolar lavage fluid is associated with acute cellular rejection after human lung transplantation.
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DOI：
10.1097/tp.0b013e3182a6ee0a
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发表时间：
2014-01-15
期刊：
影响因子：
6.2
通讯作者：
Liles WC
中科院分区：
文献类型：
--
作者：
Husain S;Resende MR;Rajwans N;Zamel R;Pilewski JM;Crespo MM;Singer LG;McCurry KR;Kolls JK;Keshavjee S;Liles WC
CXCL 10（IP-10）是一种有效的T细胞化学引诱物，在动物模型中被认为在感染和急性细胞排斥（ACR）中起作用。我们测量了肺移植受者（LTR）的支气管肺泡灌洗（BAL）中的CXCL 10（IP-10）（以及先前与ACR发病机制有关的其他细胞因子），以确定LTR中CXCL 10（IP-10）与ACR之间的关联。在85例LTR的前瞻性研究中，（TNF、IFNγ、IL-6、IL-8、IL-15、IL-16、IL-17、CXCL 10（IP-10）和MCP-1（CCL 2）），来自ACR发作（n=44）、感染（感染）（n=25）、伴随“感染+ACR”（n=10）患者的BAL样本（n=233），和“无感染且无ACR”（n=154）进行了分析。与“无感染且无ACR”组相比，组织学证实的ACR中CXCL 10（IP-10）和IL-16的水平均显着增加（CXCL10 [IP-10]：107.0 vs. 31.9 pg/mL [p=0.001]; IL-16：然而，在线性混合效应模型中，仅在CXCL 10（IP-10）]和ACR之间发现显著关联。CXCL 10（IP-10）增加1个对数与ACR风险增加40%相关（OR 1.4; 95% CI 1.12-1.84）。BAL液中较高的CXCL 10（IP-10）值与LTR中的ACR相关，表明LTR中ACR发病机制中的潜在机制作用。这些结果表明，抑制CXCL 10（IP-10）和/或其同源受体CXCR 3的治疗策略值得研究，以预防和/或治疗临床肺移植中的ACR。
CXCL10 (IP-10) is a potent chemoattractant for T cells that has been postulated to play arole in infection and acute cellular rejection (ACR) in animal models. We measured CXCL10 (IP-10) (and other cytokines previously implicated in the pathogenesis of ACR) in the bronchoalveolar lavage (BAL) of lung transplant recipients (LTRs) to determine the association between CXCL10 (IP-10) and ACR in LTRs. In a prospective study of 85 LTRs, expression of cytokines (TNF, IFNγ, IL-6, IL-8, IL-15, IL-16, IL-17, CXCL10 (IP-10) and MCP-1 (CCL2)) in BAL samples (n=233) from patients with episodes of ACR (n=44), infection (Infect) (n=25), concomitant ‘Infect +ACR’ (n=10), and ‘No Infect & No ACR’ (n=154) were analyzed. The levels of both CXCL10 (IP-10) and IL-16 were significantly increased in histologically proven ACR, as compared to the ‘No Infect & No ACR’ group (CXCL10 [IP-10]: 107.0 vs. 31.9 pg/mL [p=0.001]; IL-16: 472.1 vs. 283.01 [p=0.01]).However, in a linear mixed effects model, significant association was found only between CXCL10 (IP-10)] and ACR. A 1-log increase of CXCL10 (IP-10) was associated with a 40% higher risk of ACR (OR 1.4; 95% CI 1.12-1.84). Higher values of CXCL10 (IP-10) in BAL fluid are associated with ACR in LTRs suggesting a potential mechanistic role in the pathogenesis of ACR in LTRs. These results suggest that therapeutic strategies to inhibit CXCL10 (IP-10) and or its cognate receptor, CXCR3, warrant investigation to prevent and/or treat ACR in clinical lung transplantation.