％0期刊论文％辛普森，凯瑟琳E.％阿陈，珍妮Y.％A达米科，瑞秋L.％A哈桑，保罗M％马丁，丽莎J.％阿阳，君％A NIES，梅兰妮％一个格里菲斯，梅根％A维迪，R. Dhananjay％A Brandal，斯蒂芬妮％A Pauciulo，迈克尔W.％A卢茨，凯蒂A.％科尔曼，安娜W.％A奥斯汀，埃里克D.％A常春藤，邓巴d。%A Nichols, William C. %A Everett, Allen D. %T Cellular sources of IL-6 and associations with clinical phenotypes and outcomes in PAH %D 2020 %R 10.1183/13993003.01761-2019 %J European Respiratory Journal %P 1901761 %X The pro-inflammatory cytokine interleukin-6 (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 with 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 (HR 1.22, 95% CI 1.08–1.38, p<0.01) and in IPAH, though 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Simpson has nothing to disclose.Conflict of interest: Dr. Chen has nothing to disclose.Conflict of interest: Dr. Damico has nothing to disclose.Conflict of interest: Dr. Hassoun has nothing to disclose.Conflict of interest: Dr. Martin has nothing to disclose.Conflict of interest: Dr. Yang has nothing to disclose.Conflict of interest: Dr. Nies has nothing to disclose.Conflict of interest: Dr. Griffiths has nothing to disclose.Conflict of interest: Dr. Vaidya has nothing to disclose.Conflict of interest: Dr. Brandal has nothing to disclose.Conflict of interest: Dr. Pauciulo has nothing to disclose.Conflict of interest: Katie A. Lutz has nothing to disclose.Conflict of interest: Anna W. Coleman has nothing to disclose.Conflict of interest: Dr. Austin has nothing to disclose.Conflict of interest: Dr. Ivy has nothing to disclose.Conflict of interest: Dr. Nichols has nothing to disclose.Conflict of interest: Dr. Everett has nothing to disclose. %U //www.qdcxjkg.com/content/erj/early/2020/01/16/13993003.01761-2019.full.pdf