doi: 10.1161/01.RES.0000150734.79804.92
© 2004 American Heart Association, Inc.
Reviews |
Cytokine-Induced Modulation of Cardiac Function
From the Institute of Molecular Cardiology, Departments of Medicine and Physiology and Biophysics, University of Louisville Health Sciences Center, and Medical Service, Louisville Veterans Affairs Medical Center, Louisville, Ky.
Correspondence to Sumanth D. Prabhu, MD, Medicine/Cardiology, University of Louisville, ACB, 3rd Floor, 550 South Jackson St, Louisville, KY 40202. E-mail sprabhu{at}louisville.edu
This Review is part of a thematic series on Chemokines and Cytokines, which includes the following articles:
Inflammatory Mediators and the Failing Heart: Past, Present, and the Foreseeable Future
Inflammatory Cytokines and Postmyocardial Infarction Remodeling
Chemokines in the Pathogenesis of Vascular Disease
Cytokine-Induced Modulation of Cardiac Function
Peter Liu Guest Editor
Cytokines act in an autocrine and/or paracrine fashion to induce a diverse variety of biological responses. Several cardiac diseases are associated with cytokine activation, and such activation significantly influences several physiologic parameters, including cardiac mechanical function. This review summarizes the current concepts regarding the modulation of myocardial function by cytokines and provides rationale for the sometimes-conflicting results in the literature regarding underlying mechanisms and patterns of dysfunction. Although traditionally considered cardiodepressant mediators, contractile responses are complex and bimodal, with an early response (within minutes) of variable direction, stimulatory or depressant, depending on the ambient physiologic milieu and relative contributions of the underlying signaling pathways that are activated. These pathways include sphingomyelinase-, nitric oxide (NO)-, and phospholipase A2-dependent signaling with resultant combined effects on contraction and the Ca2+ transient. This is subsequently followed by a profoundly cardiodepressant late response lasting hours to days, depending on the production of secondary mediators and the combined influence of NO generated from inducible NO synthase, reactive oxygen species, and alterations in ß-adrenergic receptor signaling. The interrelationships between these pathways and the time-dependence of their activation are important considerations in the evaluation of cytokine-dependent dysfunction during both acute cardiac injury and chronic cardiac pathologies.
Key Words: cytokines • myocardial contraction • nitric oxide • sphingosine • free radicals
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