title: Crucial role of interleukin-6 in the development of norepinephrine-induced left ventricular remodeling in mice.
abstract: BACKGROUND
  Elevated serum concentration of interleukin (IL)-6 is a predictor for poor prognosis in congestive heart failure. It was shown previously in rats, that IL-6 expression in the left ventricle (LV) was followed by LV hypertrophy.
  
  
  METHODS
  Using IL-6 deficient mice (IL-6(-/-)), we studied the role of IL-6 in a model of norepinephrine (NE)-induced LV hypertrophy.
  
  
  RESULTS
  In wild type (WT) mice, IL-6 mRNA expression and its concentration in the serum were elevated after 4 h of NE-treatment (s.c. 0.25 mg.h)./kg Further, NE-induced LV hypertrophy was detected: LV weight/body weight (LVW/BW) ratio (+12.3+/-3%, p < 0.05) and mRNA expression of atrial natriuretic peptide (ANP) in WT mice (+120+/-25%, p < 0.05) after 3 days were increased. In contrast, NE did not induce elevation of LVW/BW ratio and ANP expression in IL-6(-/-) mice. Replacement with recombinant IL-6 restored the hypertrophy-inducing effect of NE in IL-6(-/-) mice. As to the extracellular matrix (ECM) proteins, NE increased collagen type I and III expression only in WT mice and not in IL-6(-/-) mice. The addition of recombinant IL-6 elevated the expression of the ECM proteins to the WT level.
  
  
  CONCLUSIONS
  IL-6 is a major player in the development of NE-induced LV hypertrophy in mice.
authors.affiliation: Carl-Ludwig-Institute of Physiology, University of Leipzig, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Meier
authors.forename: Jörg
authors.initials: J
authors.lastname: Bullinger
authors.forename: Grit
authors.initials: G
authors.lastname: Marx
authors.forename: Alexander
authors.initials: A
authors.lastname: Deten
authors.forename: Lars-Christian
authors.initials: LC
authors.lastname: Horn
authors.forename: Beate
authors.initials: B
authors.lastname: Rassler
authors.forename: Heinz-Gerd
authors.initials: HG
authors.lastname: Zimmer
authors.forename: Wilfried
authors.initials: W
authors.lastname: Briest
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009638:Norepinephrine; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D009320:Atrial Natriuretic Factor; D020778:Matrix Metalloproteinase 2; D009638:Norepinephrine