title: IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury.
abstract: Reperfusion of the ischemic myocardium is associated with a dramatic inflammatory response leading to TNF-alpha release, IL-6 induction, and subsequent neutrophil-mediated cytotoxic injury. Because inflammation is also an important factor in cardiac repair, we hypothesized the presence of components of the inflammatory reaction with a possible role in suppressing acute injury. Thus, we investigated the role of IL-10, an anti-inflammatory cytokine capable of modulating extracellular matrix biosynthesis, following an experimental canine myocardial infarction. Using our canine model of myocardial ischemia and reperfusion, we demonstrated significant up-regulation of IL-10 mRNA and protein in the ischemic and reperfused myocardium. IL-10 expression was first detected at 5 h and peaked following 96-120 h of reperfusion. In contrast, IL-4 and IL-13, also associated with suppression of acute inflammation and macrophage deactivation, were not expressed. In the ischemic canine heart, CD5-positive lymphocytes were the predominant source of IL-10 in the myocardial infarct. In the absence of reperfusion, no significant induction of IL-10 mRNA was noted. In addition, IL-12, a Th1-related cytokine associated with macrophage activation, was not detected in the ischemic myocardium. In vitro experiments demonstrated late postischemic cardiac-lymph-induced tissue inhibitor of metalloproteinases (TIMP)-1 mRNA expression in isolated canine mononuclear cells. This effect was inhibited when the incubation contained a neutralizing Ab to IL-10. Our findings suggest that lymphocytes infiltrating the ischemic and reperfused myocardium express IL-10 and may have a significant role in healing by modulating mononuclear cell phenotype and inducing TIMP-1 expression.
authors.affiliation: DeBakey Heart Center, Section of Cardiovascular Sciences, Department of Medicine, The Methodist Hospital, Houston, TX 77030, USA. ngf@bcm.tmc.edu
authors.forename: N G
authors.initials: NG
authors.lastname: Frangogiannis
authors.forename: L H
authors.initials: LH
authors.lastname: Mendoza
authors.forename: M L
authors.initials: ML
authors.lastname: Lindsey
authors.forename: C M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: L H
authors.initials: LH
authors.lastname: Michael
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
authors.forename: M L
authors.initials: ML
authors.lastname: Entman
mesh_terms: D000276:Adjuvants, Immunologic / Q000096:biosynthesis* / Q000502:physiology; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003001:Cloning, Molecular; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D018793:Interleukin-13 / Q000235:genetics / Q000302:isolation & purification; D015847:Interleukin-4 / Q000235:genetics / Q000302:isolation & purification; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology; D008196:Lymph / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D017202:Myocardial Ischemia / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D018793:Interleukin-13; D015850:Interleukin-6; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4