Growth factors and interleukin-6 across the lung circulation in pulmonary hypertension

The aim of our study was to assess the levels of growth factors and interleukin (IL)-6 across the pulmonary circulation in patients with pulmonary arterial hypertension (PAH) and correlate them with clinical and haemodynamic data and outcome. Simultaneous arterial and pulmonary arterial blood samples in patients with PAH (n=44) and controls (n=20) were obtained during right heart catheterisation. Vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-beta 1 and IL-6 were measured using ELISA. Arterial median (interquartile range) values for VEGF, PDGF-BB, TGF-beta 1 and IL-6 were significantly higher in patients (377 (218-588) versus 9.0 pg.mL(-1); 1,955 (1,371-2,519) versus 306 (131-502) pg.mL(-1); 26.42 (11.3-41.1) versus 7.0 (1.8-18.4) ng.mL(-1); and 3.98 (0.7-8.1) versus 0.7 pg.mL(-1), respectively; p<0.001 for all variables). There was a consistent step-up of VEGF, PDGF-BB and TGF-beta 1 across the lungs in PAH patients (p<0.001, p=0.002 and p<0.001, respectively), whereas in controls, arterial and pulmonary arterial serum levels of IL-6 and growth factors were similar (statistically nonsignificant). In multivariate analysis, increased IL-6 levels predicted mortality (hazard ratio 1.08 (95% confidence interval 1.02-1.15); p=0.012). Our findings indicate increased release and/or decreased clearance of growth factors at the lung vascular level, which may contribute to vascular remodelling in PAH.