Chronic heart failure is associated with increased interleukin-1β (IL-1β), leukocyte infiltration, and fibrosis in the heart and lungs. Here we further studied the role of IL-1β in the transition from left heart failure to pulmonary hypertension and right ventricular hypertrophy in mice with existing left heart failure produced by transverse aortic constriction. We demonstrated that transverse aortic constriction-induced heart failure was associated with increased lung inflammation and cleaved IL-1β, and inhibition of IL-1β signaling using blocking antibodies of clone B122 effectively attenuated further decrease of left ventricular systolic function in mice with existing heart failure. We found that inhibition of IL-1β attenuated lung inflammation, inflammasome activation, fibrosis, oxidative stress, and right ventricular hypertrophy. IL-1β blocking antibodies of clone B122 also significantly attenuated lung T cell activation. Together, these data indicate that IL-1β signaling exerts a causal role for heart failure progression, or the transition from left heart failure to lung remodeling and right heart hypertrophy.

慢性心力衰竭与白细胞介素-1β（IL-1β）升高，白细胞浸润以及心脏和肺部纤维化有关。在这里，我们进一步研究了IL-1β在由左主动脉狭窄引起的现有左心衰竭的小鼠中，从左心衰竭转变为肺动脉高压和右心室肥大的作用。我们证明横向主动脉缩窄引起的心力衰竭与肺炎症增加和IL-1β裂解有关，使用克隆B122的封闭抗体抑制IL-1β信号传导可有效减轻现有心力衰竭小鼠的左心室收缩功能进一步降低。我们发现抑制IL-1β可减轻肺部炎症，炎症小体激活，纤维化，氧化应激和右室肥大。克隆B122的IL-1β阻断抗体也显着减弱了肺T细胞活化。总之，这些数据表明IL-1β信号传导对心力衰竭的进展或从左心力衰竭到肺重构和右心肥大的过渡起着因果作用。