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Isolation and Identification of Extravascular Immune Cells of the Heart
Published on: August 23, 2018
Chronic heart failure and the immune system
Daniela Mari1, Federica Di Berardino, Massimo Cugno
1Department of Internal Medicine, University of Milan, Maggiore Hospital IRCCS, Via Pace 15, 20122 Milan, Italy. daniela.mari@unimi.it
Insights
Immune system activation, involving cytokines and chemokines, plays a key role in chronic heart failure (CHF) progression. Research explores gut or heart origins of this inflammation, suggesting new anti-cytokine therapies for CHF.
Area of Science:
- Cardiology
- Immunology
- Pathophysiology
Background:
- Chronic heart failure (CHF) pathogenesis involves immune mechanisms.
- Proinflammatory cytokines, chemokines, adhesion molecules, autoantibodies, nitric oxide (NO), and endothelin-1 are implicated in CHF progression.
- The precise origin of immune activation in CHF remains unclear.
Purpose of the Study:
- To investigate the role of immune mechanisms in chronic heart failure (CHF).
- To explore potential sources of immune activation in CHF.
- To identify new therapeutic strategies for CHF based on immune system modulation.
Main Methods:
- Review of existing experimental and clinical data on immune involvement in CHF.
- Analysis of proposed hypotheses regarding the origin of immune activation (gut vs. heart).
- Consideration of systemic hypoxia as a contributing factor to immune activation.
Main Results:
- Evidence supports immune system involvement in CHF, including cytokines (interleukin-1, -2, -6, tumor necrosis factor) and chemokines.
- Two main hypotheses for immune activation: bacterial translocation from bowel edema or cytokine production by the failing heart.
- Systemic hypoxia is identified as a potent stimulus for immune activation and cytokine production in CHF.
Conclusions:
- The immune system, particularly cytokines, is crucial in CHF pathogenesis.
- Neither gut nor heart alone fully explains the systemic inflammation in CHF; a multifactorial origin is likely.
- Targeting immune pathways, such as with anti-cytokine drugs, offers promising therapeutic avenues for CHF.
Abstract:
Several lines of evidence support a role of immune mechanisms in the pathogenesis of chronic heart failure (CHF). Proinflammatory cytokines (interleukin-1, -2, -6, and tumor necrosis factor) and chemokines are involved in cardiac depression and in the progression of heart failure. Other components believed to be relevant to the pathogenesis of CHF are adhesion molecules, autoantibodies, nitric oxide (NO), and endothelin-1. The origin of the immune activation in patients with CHF is still unknown, however two hypotheses have been proposed on the basis of experimental and clinical data. One suggests that the bowel wall edema leads to bacterial translocation with subsequent endotoxin release and immune activation. The second suggests that the heart in CHF is the main source of cytokines, as is shown by the fact that TNF alpha is produced by the failing myocardium but not by a normal one. No single source of cytokine production (gut or heart) seems sufficient to fully explain the multiple organ involvement and the systemic inflammation of CHF, which is probably related to systemic hypoxia, a potent stimulus for activation of the immune system and for cytokine production. The effort of define the immune system's role has opened new perspectives of therapeutic strategies, such as anti-cytokine drugs, to treat CHF.
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