title: Systemic inflammation in heart failure--the whys and wherefores.
abstract: Patients with chronic heart failure (HF) are characterized by systemic inflammation, as evident by raised circulating levels of several inflammatory cytokines with increasing levels according to the degree of disease severity. In addition to the myocardium itself, several tissues and cells can contribute to this inflammation, including leukocytes, platelets, tissue macrophages and endothelial cells. Although the mechanisms for the systemic inflammation is unknown, both infectious (e.g., endotoxins) and non-infectious (e.g., oxidative stress and hemodynamic overload) events could be operating, also including activation of Toll-like receptors as well as interaction with the neurohormone system. A growing body of evidence suggests that this systemic inflammation in chronic HF may play a role in the development and progression of this disorder, not only by promoting myocardial dysfunction, but also by inducing pathogenic consequences in other organs and tissues, thereby contributing to additional aspects of the HF syndrome such as cachexia, endothelial dysfunction and anemia. Although this inappropriate immune activation and inflammation could represent a new target for therapy in patients with chronic HF, the anti-tumor necrosis factor trials have been disappointing, and future research in this area will have to more precisely identify the most important mechanisms and actors in the immunopathogenesis of chronic HF in order to develop better immunomodulating agents for this disorder.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet University Hospital, University of Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Jan Kristian
authors.initials: JK
authors.lastname: Damås
authors.forename: Erik
authors.initials: E
authors.lastname: Oie
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D000740:Anemia / Q000209:etiology / Q000503:physiopathology; D002100:Cachexia / Q000209:etiology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism; D004731:Endotoxins / Q000502:physiology; D006333:Heart Failure / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007155:Immunologic Factors / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D007962:Leukocytes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051193:Toll-Like Receptors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D016207:Cytokines; D004731:Endotoxins; D007155:Immunologic Factors; D018836:Inflammation Mediators; D018377:Neurotransmitter Agents; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha