title: Muscular levels of proinflammatory cytokines correlate with a reduced expression of insulinlike growth factor-I in chronic heart failure.
abstract: OBJECTIVE
  Chronic heart failure (CHF) is associated with metabolic abnormalities leading to a catabolic syndrome in advanced stages of the disease. To assess the role of proinflammatory cytokines for the local expression of insulin-like growth factor-I (IGF-I) in this process, muscular and systemic levels of interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNFalpha) and IGF-I were analyzed in an animal model of CHF.
  
  
  METHODS
  Ligation of the left coronary artery or sham operation was performed in adult Wistar Kyoto rats. After 12 weeks, all animals were assessed by echocardiography and cardiac catheterization. Serum levels of IGF-I, IL-1beta, TNFalpha and IL-6 were determined by ELISA. In the quadriceps muscle, the expression of IGF-I, IGF-I receptor, IL-1beta and TNFalpha were assessed by RT-PCR and quantitative immunohistochemistry. Alterations in muscle fiber morphology were analyzed microscopically.
  
  
  RESULTS
  The local expression of IGF-I decreased significantly in animals with CHF (0.47 +/- 0.07 versus 0.77 +/- 0.09; p < 0.01). This reduction correlated with a decreased muscle fiber cross-sectional area (r = 0.62; p < 0.01) and inversely with the local expression of IL-1beta (r = -0.49; p < 0.05). IGF-I serum levels showed no significant differences between the two groups.
  
  
  CONCLUSIONS
  In CHF, the local IGF-I expression is reduced in the presence of normal serum levels of IGF-I. Both elevated proinflammatory cytokines and reduced local IGF-I expression contribute to a catabolic metabolism that may finally result in skeletal muscle atrophy and cardiac cachexia.
authors.affiliation: Cardiovascular Research, Partners Research Facility, 65 Landsdowne Street, Room 289, Cambridge, MA 02139, USA. pcschulze@rics.bwh.harvard.edu
authors.forename: P Christian
authors.initials: PC
authors.lastname: Schulze
authors.forename: Stephan
authors.initials: S
authors.lastname: Gielen
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.forename: Sven
authors.initials: S
authors.lastname: Möbius-Winkler
authors.forename: Sandra
authors.initials: S
authors.lastname: Erbs
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Rainer
authors.initials: R
authors.lastname: Hambrecht
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1