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

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

Research output: Contribution to journalArticle

214 Citations (Scopus)

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
StatePublished - Sep 1 2000
Externally publishedYes

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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

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.

IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury. / Frangogiannis, Nikolaos G.; Mendoza, L. H.; Lindsey, M. 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.
Frangogiannis NG, Mendoza LH, Lindsey ML, Ballantyne CM, Michael LH, Smith CW et al. IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury. Journal of Immunology. 2000 Sep 1;165(5):2798-2808.
Frangogiannis, Nikolaos G. ; Mendoza, L. H. ; Lindsey, M. 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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AU - Michael, L. H.

AU - Smith, C. W.

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