title: Interleukin-10 is not a critical regulator of infarct healing and left ventricular remodeling.
abstract: OBJECTIVE
  Interleukin-10 (IL-10) exerts potent anti-inflammatory actions and modulates matrix metalloproteinase expression. We hypothesized that endogenous IL-10 may regulate infarct healing and left ventricular remodeling by promoting resolution of the post-infarction inflammatory response and by modulating extracellular matrix metabolism.
  
  
  METHODS
  IL-10 null and wildtype (WT) mice underwent reperfused infarction protocols. We compared the healing response and remodeling-associated parameters between IL-10-/-and WT infarcts. In addition, we studied the effects of IL-10 on inflammatory gene synthesis by stimulated murine cardiac fibroblasts.
  
  
  RESULTS
  Infarcted IL-10-/-mice exhibited comparable mortality rates with WT animals. Although IL-10-/-mice had higher peak tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1/CCL2 mRNA levels in the infarcted heart than WT mice, both groups demonstrated timely repression of pro-inflammatory cytokine and chemokine mRNA synthesis after 24 h of reperfusion and exhibited a similar time course of resolution of the neutrophil infiltrate. IL-10 gene disruption did not alter fibrous tissue deposition and dilative remodeling of the infarcted heart. Pre-incubation with IL-10 did not modulate the pro-inflammatory phenotype of TNF-alpha-stimulated cardiac fibroblasts, failing to inhibit chemokine mRNA synthesis. In contrast, transforming growth factor (TGF)-beta1 pre-incubation suppressed interferon-gamma-inducible protein (IP)-10/CXCL10 synthesis by cardiac fibroblasts exposed to TNF-alpha.
  
  
  CONCLUSIONS
  IL-10 signaling plays a non-critical role in suppression of inflammatory mediators, resolution of the inflammatory response, and fibrous tissue deposition following myocardial infarction. This may be due to the relative selectivity of IL-10-mediated anti-inflammatory actions, with respect to cell type and stimulus. Resolution of post-infarction inflammation is likely to involve multiple overlapping regulatory mechanisms controlling various pro-inflammatory pathways activated in the infarcted myocardium.
authors.affiliation: Section of Cardiovascular Sciences, Baylor College of Medicine and the Methodist Hospital, One Baylor Plaza M/S F-602, Houston TX 77030, United States.
authors.forename: Pawel
authors.initials: P
authors.lastname: Zymek
authors.forename: Deuk-Young
authors.initials: DY
authors.lastname: Nah
authors.forename: Marcin
authors.initials: M
authors.lastname: Bujak
authors.forename: Guofeng
authors.initials: G
authors.lastname: Ren
authors.forename: Anna
authors.initials: A
authors.lastname: Koerting
authors.forename: Thorsten
authors.initials: T
authors.lastname: Leucker
authors.forename: Peter
authors.initials: P
authors.lastname: Huebener
authors.forename: George
authors.initials: G
authors.lastname: Taffet
authors.forename: Mark
authors.initials: M
authors.lastname: Entman
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Frangogiannis
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D004452:Echocardiography; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000276:immunology / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000473:pathology*; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D009504:Neutrophils / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020257:Ventricular Remodeling / Q000276:immunology*; D014945:Wound Healing
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10