Chronic heart failure and the immune system.
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.
Mari
Daniela
D
Department of Internal Medicine, University of Milan, Maggiore Hospital IRCCS, Via Pace 15, 20122 Milan, Italy. daniela.mari@unimi.it
Di Berardino
Federica
F
Cugno
Massimo
M
D002908:Chronic Disease; D016207:Cytokines / Q000097:blood / Q000276:immunology; D006333:Heart Failure / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology; D013577:Syndrome; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000276:immunology / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology
D016207:Cytokines