Crucial role of interleukin-6 in the development of norepinephrine-induced left ventricular remodeling in mice.
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.
Meier
Henning
H
Carl-Ludwig-Institute of Physiology, University of Leipzig, Germany.
Bullinger
Jörg
J
Marx
Grit
G
Deten
Alexander
A
Horn
Lars-Christian
LC
Rassler
Beate
B
Zimmer
Heinz-Gerd
HG
Briest
Wilfried
W
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*
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