How can we cure a heart "in flame"? A translational view on inflammation in heart failure

Abstract

The prevalence of chronic heart failure is still increasing making it a major health issue in the 21st century. Tremendous evidence has emerged over the past decades that heart failure is associated with a wide array of mechanisms subsumed under the term "inflammation". Based on the great success of immuno-suppressive treatments in auto-immunity and transplantation, clinical trials were launched targeting inflammatory mediators in patients with chronic heart failure. However, they widely lacked positive outcomes. The failure of the initial study program directed against tumor necrosis factor-α led to the search for alternative therapeutic targets involving a broader spectrum of mechanisms besides cytokines. We here provide an overview of the current knowledge on immune activation in chronic heart failure of different etiologies, summarize clinical studies in the field, address unresolved key questions, and highlight some promising novel therapeutic targets for clinical trials from a translational basic science and clinical perspective.

Fig. 1

Schematic overview depicting activation mechanisms of both innate and adaptive immunity and their central effector mechanism reviewed here

Fig. 2

CD4⁺ regulatory T-cells modulate the function of T-effector cells and B-cells which leads to e.g., autoantibody production which has been found to contribute to cardiac dysfunction in several heart disease. Besides their classical regulatory role on adaptive immune response they have also been demonstrated to influence monocyte differentiation, which again influences fibrosis, and to attenuate myocardial hypertrophy