Heart Failure Reviews

, Volume 15, Issue 6, pp 543–562 | Cite as

Proinflammatory cytokines in heart failure: double-edged swords

  • Mona Hedayat
  • Mohammad Jafar Mahmoudi
  • Noel R. Rose
  • Nima Rezaei


Increased circulating and intracardiac levels of proinflammatory cytokines have been associated with chronic heart failure. Following an initial insult, the increased production of proinflammatory cytokines, including TNF-α, IL-6, IL-1, and IL-18, jeopardizes the surrounding tissue through propagation of the inflammatory response and direct effects on the cardiac myocyte structure and function. Cardiac myocyte hypertrophy, contractile dysfunction, cardiac myocyte apoptosis, and extracellular matrix remodeling contribute enormously to the development and progression of chronic heart failure. Despite the identification of efficacious pharmacological regimens and introduction of mechanical interventions, chronic heart failure remains among the leading causes of mortality worldwide. To introduce novel therapeutic strategies that modulate the inflammatory response in the context of the failing heart, it is of prime importance to determine the contributions of TNF-α, IL-6, IL-1, and IL-18 in mediating cardiac adaptive and maladaptive responses, as well as delineating their downstream intracellular signaling pathways and their potential therapeutic implications.


Chronic heart failure Immunopathogenesis Cardiac myocyte hypertrophy Contractile dysfunction Cardiac myocyte apoptosis Extracellular matrix remodeling Proinflammatory cytokines 



Noel R. Rose was supported by PHS GRANT R01HL067290. We are grateful to thank Samira Hatami for her valuable assistance in preparing the figures.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Mona Hedayat
    • 1
    • 2
  • Mohammad Jafar Mahmoudi
    • 1
  • Noel R. Rose
    • 3
  • Nima Rezaei
    • 2
    • 4
    • 5
  1. 1.Division of Cardiology, Department of Internal Medicine, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Research Group for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical CenterTehran University of Medical SciencesTehranIran
  3. 3.Johns Hopkins Center For Autoimmune Disease ResearchJohns Hopkins UniversityBaltimoreUSA
  4. 4.Department of Infection and Immunity, School of Medicine and Biomedical SciencesThe University of SheffieldSheffieldUK
  5. 5.Children’s Medical Center HospitalTehran University of Medical SciencesTehranIran

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