Circulating Interleukin-7 in Human Pulmonary Arterial Hypertension

Background: Emerging evidence suggests that natural killer (NK) cells and regulatory T-cells (Tregs, CD4+) play protective immune-modulatory roles in pulmonary arterial hypertension (PAH) and associated right ventricular dysfunction (RVD). Interleukin-7 (IL-7) forms a heterodimer with HGF and secures B-cell maturation, T- and NK-cell survival, and homeostasis. However, the role and potential impact of IL-7 on the pathobiology and severity of PAH are unknown.

Method: We recruited 10 pediatric patients with moderate PH (age range: 3.9–18.5 years) and 10 non-PH controls (age range: 2.0–17.3 years). EDTA blood was collected during cardiac catheterization from the superior vena cava (SVC), pulmonary artery (PA), and ascending aorta (AAO). Compartment-specific plasma concentrations of IL-7, VEGF-C, aldosterone, ICAM-1, and VCAM-1 were determined using the Meso Scale Discovery's multi array technology and the LIAISON Aldosterone Assay.

Results: Children with PH had approximately 50% lower IL-7 concentrations (SVC: 6.61 ± 1.04 vs. 13.25 ± 1.10 pg/mL; p < 0.001) and 59% lower VEGF-C plasma levels in the SVC, PA, and AAO versus non-PH controls. Both IL-7 (rho = −0.51; p = 0.026) and VEGF-C (r = −0.62; p = 0.0034) plasma concentrations correlated negatively with the pulmonary vascular resistance (PVR)/systemic vascular resistance (SVR) ratio. Transpulmonary gradient analysis revealed that most patients had a step down in ICAM-1 (p = 0.044) and VCAM-1 (p = 0.079) plasma concentrations across the pulmonary circulation.

Conclusion: This is the first report on decreased circulating IL-7 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 at multiple locations (circulation, pulmonary vascular/lymph vessels, and RV myocardium) in pediatric and adult PAH.

Publication History

Article published online:
12 February 2022