title: When are pro-inflammatory cytokines SAFE in heart failure?
abstract: The cytokine hypothesis presently suggests that an excessive production of pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF) and interleukin 6 (IL6), contributes to the pathogenesis of heart failure. The concept, successfully proved in genetically modified animal models, failed to translate to humans. Recently, accumulation of apparently paradoxical experimental data demonstrates that, under certain conditions, production of pro-inflammatory cytokines can initiate the activation of a pro-survival cardioprotective signalling pathway. This novel path that involves the activation of a transcription factor, signal transducer and activator of transcription 3 (STAT3), has been termed the survival activating factor enhancement (SAFE) pathway. In this review, we will discuss whether targeting the SAFE pathway may be considered as a preventive and/or therapeutic measure for the treatment of heart failure.
authors.affiliation: Hatter Cardiovascular Research Institute, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. sandrine.lecour@uct.ac.za
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lecour
authors.forename: Richard W
authors.initials: RW
authors.lastname: James
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000209:etiology* / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D051381:Rats; D018121:Receptors, Cytokine / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D016207:Cytokines; D015850:Interleukin-6; D018121:Receptors, Cytokine; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D048069:Tumor Necrosis Factors