IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury

N. G. Frangogiannis, L. H. Mendoza, Merry L Lindsey, C. M. Ballantyne, L. H. Michael, C. W. Smith, M. L. Entman

Research output: Contribution to journalArticle

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Abstract

Reperfusion of the ischemic myocardium is associated with a dramatic inflammatory response leading to TNF-α 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.

Original languageEnglish (US)
Pages (from-to)2798-2808
Number of pages11
JournalJournal of Immunology
Volume165
Issue number5
DOIs
StatePublished - Sep 1 2000

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Interleukin-10
Myocardium
Wounds and Injuries
Canidae
Reperfusion
Tissue Inhibitor of Metalloproteinase-1
Messenger RNA
Myocardial Infarction
Lymphocytes
Cytokines
Inflammation
Myocardial Reperfusion
Interleukin-13
Macrophage Activation
Lymph
Interleukin-12
Interleukin-4
Myocardial Ischemia
Extracellular Matrix
Interleukin-6

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Frangogiannis, N. G., Mendoza, L. H., Lindsey, M. L., Ballantyne, C. M., Michael, L. H., Smith, C. W., & Entman, M. L. (2000). IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury. Journal of Immunology, 165(5), 2798-2808. https://doi.org/10.4049/jimmunol.165.5.2798

IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury. / Frangogiannis, N. G.; Mendoza, L. H.; Lindsey, Merry L; Ballantyne, C. M.; Michael, L. H.; Smith, C. W.; Entman, M. L.

In: Journal of Immunology, Vol. 165, No. 5, 01.09.2000, p. 2798-2808.

Research output: Contribution to journalArticle

Frangogiannis, NG, Mendoza, LH, Lindsey, ML, Ballantyne, CM, Michael, LH, Smith, CW & Entman, ML 2000, 'IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury', Journal of Immunology, vol. 165, no. 5, pp. 2798-2808. https://doi.org/10.4049/jimmunol.165.5.2798
Frangogiannis, N. G. ; Mendoza, L. H. ; Lindsey, Merry L ; Ballantyne, C. M. ; Michael, L. H. ; Smith, C. W. ; Entman, M. L. / IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury. In: Journal of Immunology. 2000 ; Vol. 165, No. 5. pp. 2798-2808.
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