Inflammatory mediators and the failing heart: A translational approach

Abhinav Diwan, Tony Tran, Arunima Misra, Douglas L. Mann

Research output: Contribution to journalArticle

72 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)161-182
Number of pages22
JournalCurrent Molecular Medicine
Volume3
Issue number2
DOIs
StatePublished - Mar 2003
Externally publishedYes

Fingerprint

Heart Failure
Cytokines
Tumor Necrosis Factor-alpha
Clinical Trials
Interleukin-1
Multicenter Studies
Disease Progression
Interleukin-6
Myocardium
Health
Wounds and Injuries
Growth
Molecules

Keywords

  • [110] congestive heart failure
  • [147] growth factors/cytokines
  • Clinical trials
  • Etanercept
  • Inflammatory mediators
  • Infliximab
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Biochemistry

Cite this

Inflammatory mediators and the failing heart : A translational approach. / Diwan, Abhinav; Tran, Tony; Misra, Arunima; Mann, Douglas L.

In: Current Molecular Medicine, Vol. 3, No. 2, 03.2003, p. 161-182.

Research output: Contribution to journalArticle

Diwan, Abhinav ; Tran, Tony ; Misra, Arunima ; Mann, Douglas L. / Inflammatory mediators and the failing heart : A translational approach. In: Current Molecular Medicine. 2003 ; Vol. 3, No. 2. pp. 161-182.
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