title: Neutralization of interleukin-1beta in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling.
abstract: OBJECTIVE
  We sought to examine the role of the pro-inflammatory cytokine, interleukin-1-beta (IL-1beta), in the process of left ventricular (LV) remodeling in the early phase after myocardial infarction (MI).
  
  
  BACKGROUND
  Studies have shown that pro-inflammatory cytokines are closely related to the progression of LV remodeling after MI.
  
  
  METHODS
  Mice underwent coronary artery ligation, and the time course of LV remodeling was followed up to 20 weeks. The gene expression level of IL-1beta was examined. In a second set of experiments, the mice underwent coronary artery ligation followed by treatment with anti-IL-1beta antibody (100 microg, intravenously), versus control immunoglobulin G (100 microg, intravenously) immediately after the operation.
  
  
  RESULTS
  Rapid hypertrophy of noninfarcted myocardium was observed by four weeks, and interstitial fibrosis progressed steadily up to 20 weeks. Anti-IL-1beta treatment increased the occurrence of ventricular rupture and suppressed collagen accumulation in the infarct-related area. At four and eight weeks after the operation, total heart weight and LV end-diastolic dimension were significantly greater in the anti-IL-1beta-treated mice than in the other groups. In the infarct-related area, collagen accumulation was suppressed, whereas in the noninfarcted area, pro-collagen gene expression levels, particularly type III, were decreased in the anti-IL-1beta-treated mice.
  
  
  CONCLUSIONS
  Anti-IL-1beta treatment suppressed pro-collagen gene expression and delayed wound healing mechanisms-properties that are likely to lead to progression of LV remodeling. In the acute phase of MI, IL-1beta appears to play a protective role.
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: M W
authors.initials: MW
authors.lastname: Hwang
authors.forename: A
authors.initials: A
authors.lastname: Matsumori
authors.forename: Y
authors.initials: Y
authors.lastname: Furukawa
authors.forename: K
authors.initials: K
authors.lastname: Ono
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: A
authors.initials: A
authors.lastname: Iwasaki
authors.forename: M
authors.initials: M
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Miyamoto
authors.forename: M
authors.initials: M
authors.lastname: Touma
authors.forename: S
authors.initials: S
authors.lastname: Sasayama
mesh_terms: D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D002423:Cause of Death; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D017548:Echocardiography, Transesophageal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006439:Hemodynamics / Q000187:drug effects; D007249:Inflammation; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D011897:Random Allocation; D051381:Rats; D016019:Survival Analysis; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007375:Interleukin-1