Cytokine-Induced Modulation of Cardiac Function
Top Cited Papers
- 10 December 2004
- journal article
- review article
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 95 (12), 1140-1153
- https://doi.org/10.1161/01.res.0000150734.79804.92
Abstract
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 β-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.Keywords
This publication has 98 references indexed in Scilit:
- Nitric Oxide Protects Against Pathological Ventricular RemodelingCirculation Research, 2004
- N -Acetylcysteine Prevents the Deleterious Effect of Tumor Necrosis Factor-α on Calcium Transients and Contraction in Adult Rat CardiomyocytesCirculation, 2004
- Endotoxin and Tumor Necrosis FactorαExert a Similar Proinflammatory Effect in Neonatal Rat Cardiomyocytes, but have Different Cardiodepressant Profiles,Journal of Molecular and Cellular Cardiology, 1998
- Regulation of Cytokine-inducible Nitric Oxide Synthase in Cardiac Myocytes and Microvascular Endothelial Cells: ROLE OF EXTRACELLULAR SIGNAL-REGULATED KINASES 1 AND 2 (ERK1/ERK2) AND STAT1αPublished by Elsevier ,1996
- TNFα receptor expression in rat cardiac myocytes: TNFα inhibition of L‐type Ca2+ current and Ca2+ transientsFEBS Letters, 1995
- Effects of cytokines on the contractility of cultured cardiac myocytesInternational Journal of Immunopharmacology, 1993
- Interleukin-6 (IL-6) as a mediator of stunned myocardiumThe American Journal of Cardiology, 1993
- Positive inotropic effect of interleukin-2. Role of phospholipases and protein kinase CInternational Journal of Immunopharmacology, 1991
- Tumor necrosis factor α up-regulates Giα and Gß proteins and adenylyl cyclase responsiveness in rat cardiomyocytesEuropean Journal of Pharmacology: Molecular Pharmacology, 1991
- Stimulation of heart contractility by supernatants from lectin-activated lymphocytes. Role of IL-2International Journal of Immunopharmacology, 1989