Rationale Previously we showed that human plasma IL7, protein levels of IL7 receptor (IL7R) in total lung homogenate and pulmonary artery endothelial cells (PAECs)/PASMCs were significantly elevated in PAH patients. IL7 promotes PASMC proliferation. IL7R-deficient (IL7R−/−) mice are protected from hypoxia-mediated pulmonary hypertension (HPH). We sought to study whether blocking IL7 via anti-IL7 antibodies can reverse experimental PH in mice.
Methods Male C57BL/6 mice (7 week old) were exposed to normoxia or hypoxia (10% O2) for 4 weeks (n=6 per group). At Day 12 after hypoxia exposure, a monoclonal antibody against IL7 (AB-407-na, R&D Systems) or control IgG was started to treat the mice (100 µg/mouse, every other day, IP, for two weeks). Right ventricular systolic pressure (RVSP) was determined with a Millar pressure transducer catheter. The right ventricle: left ventricle +septum (RV/LV+S) ratio was calculated. Pulmonary artery remodeling was assessed using Aperio image software.
Result After four weeks of hypoxic exposure, treatment of IL7 antibody significantly attenuated RVSP (28.89±0.87 vs. 34.43±2.23 mm Hg, p=0.03), developed less right ventricular hypertrophy (RVH) (RV/LV+S 0.29±0.0087 vs. 0.39±0.014, p=0.0002), and lower pulmonary arterial thickness when compared to control-IgG treated group.
Conclusion IL7 antibodies reverse HPH in mice. IL7 antibodies could be a novel therapeutic candidate for pulmonary hypertension.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.