Inflammatory Mediators and the Failing Heart: A Translational Approach

Authors: Diwan A.; Tran T.; Misra A.; Mann D.L.

Source: Current Molecular Medicine, Volume 3, Number 2, March 2003 , pp. 161-182(23)

Publisher: Bentham Science Publishers

Key:
Free Content - Free Content
New Content - New Content
Subscribed Content - Subscribed Content
Free Trial Content - Free Trial Content

Abstract:

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.

MeSH-Medline keywords: [110] congestive heart failure, [147] growth factors / cytokines, tumor necrosis factor, inflammatory mediators, clinical trial, etanercept, infliximab.

Keywords: proinflammatory mediators; myocardium; tumor necrosis factor (TNF); congestive heart failure; infliximab; cytokines

Language: English

Document Type: Review article

DOI: 10.2174/1566524033361537

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$55.10 plus tax      Refund Policy

 

OR

Back to top

Key:
Free Content - Free Content
New Content - New Content
Subscribed Content - Subscribed Content
Free Trial Content - Free Trial Content
Share this item with others: These icons link to social bookmarking sites where readers can share and discover new web pages.
Page Help Click here for Page Help
Shopping cart
Tools
Sign in






Need to register?
Sign up here
Text size: A | A | A | A