[Cytokines--causes, players or bystanders in heart failure].
BACKGROUND
Cytokines are important mediators of the immune system and are of pathophysiological relevance for different cardiac diseases. Currently, 18 cytokines carrying the name interleukin (IL) are known; they can be subdivided into pro- and anti-inflammatory interleukins.
They partly act in a negative inotropic manner and cause destruction of cardiomyocytes resulting in myocardial fibrosis. The proinflammatory cytokine tumor necrosis factor (TNF-)alpha induces cardiodepressive effects and causes apoptosis. TNF-alpha, IL-6, soluble TNF-receptor-1 and -2 are independent predictors of increased mortality of patients with heart failure. Experimental and clinical evidence has shown that plasma and tissue levels of TNF-alpha were elevated to such extent as to explain at least some of the symptoms of heart failure due to the actions of this cytokine.


RESULTS
Two multicenter studies (RENAISSANCE, RECOVER), based on promising pilot studies, have disclosed no effect for the TNF-alpha antagonists (Etanercept) on mortality and morbidity. It is not possible, however, to draw the conclusion from the data of these studies that TNF-alpha plays no significant pathophysiological role in the etiology and progression of heart failure.
Staudt
Alexander
A
Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität Greifswald, Germany.
Landsberger
Martin
M
Staudt
Yvonne
Y
Felix
Stephan B
SB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000209:etiology; D017322:Clinical Trials, Phase II as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000097:blood / Q000502:physiology*; D004311:Double-Blind Method; D000068800:Etanercept; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use; D000069285:Infliximab; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000097:blood / Q000502:physiology; D051379:Mice; D008970:Molecular Weight; D015337:Multicenter Studies as Topic; D010431:Pentoxifylline / Q000008:administration & dosage / Q000627:therapeutic use; D010919:Placebos; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000502:physiology / Q000627:therapeutic use; D016019:Survival Analysis; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D016207:Cytokines; D007074:Immunoglobulin G; D015850:Interleukin-6; D007378:Interleukins; D010919:Placebos; D018124:Receptors, Tumor Necrosis Factor; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept; D010431:Pentoxifylline