Cellular sources of interleukin-6 and associations with clinical phenotypes and outcomes in pulmonary arterial hypertension.
Cellular sources of interleukin-6 and associations with clinical phenotypes and outcomes in pulmonary arterial hypertension.
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DOI：
10.1183/13993003.01761-2019
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发表时间：
2020-04
期刊：
影响因子：
--
通讯作者：
Everett AD
中科院分区：
文献类型：
--
作者：
Simpson CE;Chen JY;Damico RL;Hassoun PM;Martin LJ;Yang J;Nies M;Griffiths M;Vaidya RD;Brandal S;Pauciulo MW;Lutz KA;Coleman AW;Austin ED;Ivy DD;Nichols WC;Everett AD
促炎细胞因子白细胞介素 (IL)-6 与主要由严重特发性 PAH (IPAH) 患者组成的小型肺动脉高压 (PAH) 队列的结果相关。目前尚不清楚 IL-6 是否是危重疾病的标志物或肺血管重塑的机械生物标志物。我们假设 IL-6 由肺血管细胞产生，并试图在大型 PAH 队列中探索 IL-6 与不同亚型的表型和结果的关联。测量来自 PAH 患者和健康对照的培养的肺动脉平滑肌细胞 (PASMC) 和内皮细胞 (PAEC) 中的 IL-6 蛋白和基因表达水平。在代表每个 PAH 亚组的 2017 年特征明确的 PAH 受试者中测量了血清 IL-6。使用回归模型分析 IL-6 水平、临床变量和死亡率之间的关系。在 PAH 中，PASMC 产生的 IL-6 蛋白和基因表达水平显着高于 PAEC（p<0.001），而对照细胞类型之间的 IL-6 没有差异。血清IL-6在与门脉高压和结缔组织病相关的PAH（CTD-PAH）中最高。在多变量模型中，血清 IL-6 与整个队列（风险比 1.22，95% CI 1.08-1.38；p<0.01）和 IPAH 中的生存相关，但与 CTD-PAH 中的生存无关。 IL-6 仍然与患有轻度疾病的低风险亚组患者的生存相关。 IL-6 由 PASMC 释放，循环中的 IL-6 与各种 PAH 亚组（包括病情较轻的受试者）的特定临床表型和结果相关。 IL-6 是一种机械生物标志物，因此是某些 PAH 亚组的潜在治疗靶点。
The pro-inflammatory cytokine interleukin (IL)-6 has been associated with outcomes in small pulmonary arterial hypertension (PAH) cohorts composed largely of patients with severe idiopathic PAH (IPAH). It is unclear whether IL-6 is a marker of critical illness or a mechanistic biomarker of pulmonary vascular remodelling. We hypothesised that IL-6 is produced by pulmonary vascular cells and sought to explore IL-6 associations with phenotypes and outcomes across diverse subtypes in a large PAH cohort. IL-6 protein and gene expression levels were measured in cultured pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) from PAH patients and healthy controls. Serum IL-6 was measured in 2017 well-characterised PAH subjects representing each PAH subgroup. Relationships between IL-6 levels, clinical variables, and mortality were analysed using regression models. Significantly higher IL-6 protein and gene expression levels were produced by PASMCs than by PAECs in PAH (p<0.001), while there was no difference in IL-6 between cell types in controls. Serum IL-6 was highest in PAH related to portal hypertension and connective tissue diseases (CTD-PAH). In multivariable modelling, serum IL-6 was associated with survival in the overall cohort (hazard ratio 1.22, 95% CI 1.08–1.38; p<0.01) and in IPAH, but not in CTD-PAH. IL-6 remained associated with survival in low-risk subgroups of subjects with mild disease. IL-6 is released from PASMCs, and circulating IL-6 is associated with specific clinical phenotypes and outcomes in various PAH subgroups, including subjects with less severe disease. IL-6 is a mechanistic biomarker, and thus a potential therapeutic target, in certain PAH subgroups.
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影响因子：
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作者：
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影响因子：
5.8
作者：
Savale L;Tu L;Rideau D;Izziki M;Maitre B;Adnot S;Eddahibi S
通讯作者：
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DOI：
10.1016/j.healun.2017.08.011
发表时间：
2018-03
期刊：
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
影响因子：
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作者：
Prins KW;Archer SL;Pritzker M;Rose L;Weir EK;Sharma A;Thenappan T
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