title: Targeting the vicious inflammation-oxidative stress cycle for the management of heart failure.
abstract: Oxidative stress and inflammation are each implicated independently in the development and progression of heart failure. Their interaction, however, is also evident throughout the process from initial injury to cardiac remodeling and failure. In the failing heart, the linkage between excessive reactive oxygen species (ROS) and the cytokine elaboration is manifested in shared elements and cross-promotion within downstream signaling pathways. In spite of this, the failure of anticytokine immunotherapy and antioxidant therapy, which had previously shown promise, suggests that a more complete perspective of ROS-cytokine interaction is required. The present review focuses on two of the major cytokines that are demonstrably connected to oxidative stress--the pro-inflammatory tumor necrosis factor-alpha (TNF-alpha) and the anti-inflammatory interleukin-10 (IL-10)--and their interactions in cardiac remodeling and failure. It is proposed that an optimal balance between TNF-alpha and IL-10 may be of crucial importance in mitigating both inflammation and oxidative stress processes leading to heart failure.
authors.affiliation: Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Neelam
authors.initials: N
authors.lastname: Khaper
authors.forename: Sean
authors.initials: S
authors.lastname: Bryan
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Dhingra
authors.forename: Rohit
authors.initials: R
authors.lastname: Singal
authors.forename: Anju
authors.initials: A
authors.lastname: Bajaj
authors.forename: Chander M
authors.initials: CM
authors.lastname: Pathak
authors.forename: Pawan K
authors.initials: PK
authors.lastname: Singal
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002316:Cardiotonic Agents / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D032383:Myocytes, Cardiac / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D016207:Cytokines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10