There are currently no specific treatments for cardiac fibrosis. We tested the efficacy of a neutralising anti-IL11 antibody (X203) to reduce cardiac fibrosis in two preclinical models: transverse aortic constriction (TAC) and chronic angiotensin II infusion (AngII). In the first model, male C57BL/6J mice were subjected to TAC for 2 weeks. In the second model, mice received continuous angiotensin II for 4 weeks via subcutaneous pump. In both models, mice received either 20 mg/kg of X203 or isotype-control antibody twice-weekly, starting 24 h after surgery. Cardiac fibrosis and extracellular matrix gene expression were assessed by RT-qPCR, Western blot, histology and collagen (hydroxyproline) assays. In both models, X203 significantly reduced pro-fibrotic gene expression and myocardial fibrosis (TAC: 51% reduction in total collagen, P < 0.001, 39% in perivascular fibrosis, P < 0.001; AngII: 17% reduction in total collagen, P = 0.04, 83% in perivascular fibrosis, P < 0.001). Pharmacological targeting of IL11 reduces cardiac fibrosis in preclinical models. Figa Graphical Abstract.
Keywords: Angiotensin II; Cardiac; Fibrosis; Interleukin-11; Transverse-aortic constriction.