Circulating Interleukin-7 in Human Pulmonary Arterial Hypertension

Abstract

Objectives: Interleukin-7 (IL-7) secures B cell maturation, regulatory T and natural killer (NK) cell survival, and homeostasis, all of which are important for beneficial immunomodulation in pulmonary arterial hypertension (PAH). However, the role and potential impact of IL-7, VEGF-C and the vascular injury markers ICAM-1, and VCAM-1 on the pathobiology and severity of PAH is unknown. Methods: EDTA blood was collected during cardiac catheterization from the superior vena cava (SVC), pulmonary artery (PA), and ascending aorta (AAO) in children with pulmonary hypertension (PH) [n = 10; 9.1 (3.9–18.5) years] and non-PH controls [n = 10; 10.5 (2.0–17.3) years]. Compartment-specific plasma concentrations of IL-7, VEGF-C, aldosterone, ICAM-1, and VCAM-1 were determined using Meso Scale Discovery's multi array technology and the LIAISON Aldosterone Assay. Results: Children with PH had approximately 50% lower IL-7 (p < 0.01) and 59% lower VEGF-C plasma levels (p < 0.001) in the SVC, PA, and AAO versus non-PH controls. IL-7 and VEGF-C concentrations negatively correlated with the pulmonary vascular resistance (PVR)/systemic vascular resistance (SVR) ratio (rho = −0.51 and r = −0.62, respectively). Central-venous IL-7 strongly positively correlated with VEGF-C (r = 0.81). Most patients had a step down in ICAM-1 and VCAM-1 plasma concentrations across the pulmonary circulation and both ICAM-1 and VCAM-1 transpulmonary gradients negatively correlated with invasive hemodynamics. Conclusion: This manuscript is the first report on decreased circulating IL-7 and VEGF-C plasma concentrations in human PAH and their inverse correlations with invasive surrogates of PAH severity. Additional and larger studies are needed to explore the role of the immune-modulatory IL-7 and VEGF-C in pediatric and adult PAH.