The duality of chemokines in heart failure

Abstract

The failing human heart is a bustling network of intra- and inter-cellular signals and related processes attempting to coordinate a repair mechanism for the injured or diseased myocardium. While our understanding of signaling by mode of cytokines is well understood on a systemic level, we are only now coming to elucidate the role of cytokines in cardiac self-regulation. An increasing number of studies are showing now that cardiomyocytes themselves have not only the ability but also the mandate to produce signals, and play direct roles in how these signals are interpreted. One of the families of cytokines employed by distressed cardiac tissue are chemokines. By regulating the movement of pro-inflammatory cell types to sites of injury, we see now how the myocardium responds to stress. Herein we review the participation of these inflammatory mediators and explore the delicate balance between their protective roles and damaging functions.

Keywords:

• anti-cytokine therapies
• chemokines
• clinical trials
• cytokines
• heart failure
• stem cell-based cytokine therapies

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• The present review provides a critical overview of the clinical status of immunotherapy in patients with a failing heart.

• The duality of chemokines has been at times confounding, yet the ability of the same axis to play opposite roles suggests that these signals operate differently depending on the injury or disease environment.

• A related strategy for cardiac repair involves stem cell mobilization with factors such as cytokines/chemokines (stem cell-based cytokine therapies).

• There has been an interest in anti-cytokine therapy to improve myocardial performance; however, past clinical trials have failed to show any clinical benefits.