TY -的T1 -细胞的白细胞介素- 6的一个来源nd associations with clinical phenotypes and outcomes in pulmonary arterial hypertension JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01761-2019 VL - 55 IS - 4 SP - 1901761 AU - Simpson, Catherine E. AU - Chen, Jenny Y. AU - Damico, Rachel L. AU - Hassoun, Paul M. AU - Martin, Lisa J. AU - Yang, Jun AU - Nies, Melanie AU - Griffiths, Megan AU - Vaidya, R. Dhananjay AU - Brandal, Stephanie AU - Pauciulo, Michael W. AU - Lutz, Katie A. AU - Coleman, Anna W. AU - Austin, Eric D. AU - Ivy, Dunbar D. AU - Nichols, William C. AU - Everett, Allen D. Y1 - 2020/04/01 UR - //www.qdcxjkg.com/content/55/4/1901761.abstract N2 - 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.Circulating IL-6, a pro-inflammatory cytokine produced by pulmonary arterial smooth muscle cells, is significantly associated with clinical phenotypes and survival in pulmonary arterial hypertension, which may guide individualised disease management https://bit.ly/3awkkSz ER -