Abstract 12506: Blockade of Interleukin-6 Signaling Prevents Hypoxia Induced Pulmonary Hypertension in Mice
Background: Inflammatory cytokine interleukin-6 (IL-6) is elevated in the serum and the lungs of the patients with pulmonary arterial hypertension (PAH). Additionally, lung-specific transgenic mice overexpressing IL-6 spontaneously developed pulmonary vascular remodeling and pulmonary hypertension (PH). Here, we examined whether anti-mouse IL-6 receptor rat monoclonal antibody (MR16-1) prevents hypoxia-induced PH in mice.
Methods and Results: C57BL6 mice at age of 8 weeks were exposed to 10% O2 hypoxia for 4 weeks. The expression level of IL-6 significantly increased in the lungs after exposure to hypoxia. To determine the effect of MR16-1-mediated blockade of IL-6 signaling, mice were intravenously injected with 2mg of MR16-1 (MR16-1 group) or rat IgG (control group) just before the exposure to hypoxia, and were also injected intraperitoneally with 0.5mg of MR16-1 or rat IgG once a week, respectively. After 4-week exposure to hypoxia, the mice were subjected to hemodynamic recording and sacrificed for pathological analysis of hearts and lungs. Right ventricular (RV) systolic pressure, RV hypertrophy, and the medial wall thickness of pulmonary vessels were significantly decreased in MR16-1 group compared to control group.
Conclusion: The blockade of IL-6 signaling might become a promising strategy for the treatment of PAH.
- © 2013 by American Heart Association, Inc.