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Proinflammatory cytokines in heart failure: double-edged swords

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Division of Cardiology, Department of Internal Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mona Hedayat & Mohammad Jafar Mahmoudi

  2. Research Group for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Mona Hedayat & Nima Rezaei

  3. Johns Hopkins Center For Autoimmune Disease Research, Johns Hopkins University, Baltimore, MD, USA

    Noel R. Rose

  4. Department of Infection and Immunity, School of Medicine and Biomedical Sciences, The University of Sheffield, Sheffield, UK

    Nima Rezaei

  5. Children’s Medical Center Hospital, Tehran University of Medical Sciences, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194, Iran

    Nima Rezaei

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  1. Mona Hedayat
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  2. Mohammad Jafar Mahmoudi
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  3. Noel R. Rose
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  4. Nima Rezaei
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Correspondence to Nima Rezaei.

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Hedayat, M., Mahmoudi, M.J., Rose, N.R. et al. Proinflammatory cytokines in heart failure: double-edged swords. Heart Fail Rev 15, 543–562 (2010). https://doi.org/10.1007/s10741-010-9168-4

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