Pharmacological inhibition of IL12β is effective in treating pressure overload-induced cardiac inflammation and heart failure.

Background And Objective: Emerging evidence indicates that inflammation regulates cardiac remodeling and heart failure (HF). IL12β is a subunit for proinflammatory cytokines IL12 and IL23. However, the effect of IL12β inhibition on HF development and the underlying mechanism is not understood.

Methods: We determined the effect of pharmacological inhibition of IL12β using IL12β blocking antibody on transverse aortic constriction (TAC)-induced left ventricular (LV) inflammation and HF development.

Results: IL12β blocking antibody significantly attenuated TAC-induced LV immune cell infiltration, hypertrophy, fibrosis, dysfunction, and the consequent pulmonary inflammation and remodeling. More specifically, we found that IL12β blocking antibody significantly attenuated TAC-induced LV and pulmonary infiltration of neutrophils, macrophages, CD11c dendritic cells, CD8 T cells, and CD4 T cells. Moreover, IL12β blocking antibody significantly suppressed the production of pro-inflammatory cytokine pro-IL1β and IFNγ by macrophages and IFNγ by CD8 T cells and/or CD4 T cells.

Conclusions: These findings indicate that pharmacological inhibition of IL12β effectively protected the heart from systolic overload-induced inflammation, remodeling, and dysfunction by reducing the proinflammatory signaling from both innate and adaptive immune responses.