title: Role of interleukin-6 for LV remodeling and survival after experimental myocardial infarction.
abstract: Circulating levels of interleukin (IL)-6 are elevated after myocardial infarction (MI) and associated with increased morbidity and mortality. Its myocardial expression post-MI suggests a pathophysiological role in this condition. To explore the role of endogenous IL-6, we analyzed MI size, left ventricular (LV) remodeling, and mortality after permanent coronary ligation in IL-6 knockout mice (IL-6-/-) and wild-type controls (WT). Six weeks after MI, IL-6-/- and WT had similar mortality rates, MI sizes, LV remodeling, and LV dysfunction in vivo, determined by catheterization. Infarct size 24 h post-MI, shown by 2,3,5-triphenyltetrazolium chloride (TTC) staining, was similar at 24 h. Treatment with exogenous IL-6 did not alter MI size in WT. Infarction resulted in marked phosphorylation of STAT3, without differences between genotypes. Leukemia inhibitory factor (LIF) protein was increased 48 h post-MI in IL-6-/-, and angiotensin II and AT1 receptor (AT1R) protein were strongly increased in IL-6-/- baseline and post-MI, suggesting compensatory up-regulation. Lack of IL-6 does not affect long-term MI size or LV function, remodeling, and survival. In mice lacking IL-6, other members of the IL-6 family such as LIF and other factors signaling via JAK/STAT such as angiotensin may act in a compensatory manner to activate the JAK/STAT pathway, thereby maintaining STAT3 phosphorylation, which is crucial for the cellular effects of IL-6 cytokines.
authors.affiliation: Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Fuchs
authors.forename: Andres
authors.initials: A
authors.lastname: Hilfiker
authors.forename: Karol
authors.initials: K
authors.lastname: Kaminski
authors.forename: Denise
authors.initials: D
authors.lastname: Hilfiker-Kleiner
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Guener
authors.forename: Gunnar
authors.initials: G
authors.lastname: Klein
authors.forename: Edith
authors.initials: E
authors.lastname: Podewski
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schieffer
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
mesh_terms: D000818:Animals; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D015996:Survival Rate; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis; D020257:Ventricular Remodeling
chemical_list: D015850:Interleukin-6