4.4 Review

Inflammatory mediators and the failing heart: A translational approach

Journal

CURRENT MOLECULAR MEDICINE
Volume 3, Issue 2, Pages 161-182

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1566524033361537

Keywords

[110] congestive heart failure; [147] growth factors/cytokines; tumor necrosis factor; inflammatory mediators; clinical trial; etanercept; infliximab

Funding

  1. NHLBI NIH HHS [HL-42250-10/10, P50 HL-O6H, R01 HL58081-01, R01 HL61543-01] Funding Source: Medline

Ask authors/readers for more resources

Recent studies have identified the importance of proinflammatory mediators in regulating cardiac structure in health and disease. Recent studies suggest that cytokines that are expressed within the myocardium in response to a environmental injury, namely tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) and the interleukin-6 (IL-6) family of cytokines play an important role in initiating and integrating homeostatic responses within the heart. However, these stress-activated cytokines all have the potential to produce cardiac decompensation when expressed at sufficiently high concentrations. Indeed, there is now a growing appreciation that these molecules may play an important role in mediating disease progression in the failing heart. The growing appreciation of the pathophysiological consequences of sustained expression of proinflammatory mediators in pre-clinical and clinical, heart failure models culminated in a series of multicenter clinical trials that utilized targeted approaches to neutralize tumor necrosis factor (TNF) in patients with moderate to advanced heart failure. However, these targeted approaches have resulted in worsening heart failure, thereby raising a number of important questions about what role, if any, proinflammatory cytokines play in the pathogenesis of heart failure. This review will summarize the tremendous growth of knowledge that has taken place in this field, with a focus on what we have learned from the negative clinical trials, as well as the potential direction of future research in this area.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.4
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available