Interleukin-23 deficiency leads to impaired wound healing and adverse prognosis after myocardial infarction

Circ Heart Fail. 2014 Jan;7(1):161-71. doi: 10.1161/CIRCHEARTFAILURE.113.000604. Epub 2013 Dec 3.


Background: CD4+ cells are implicated in the healing process after myocardial infarction (MI). We sought to investigate the role of interleukin-23 (IL-23) deficiency, a cytokine important in differentiation of CD4+ cells, in scar formation of the ischemic heart.

Methods and results: MI was performed in wild-type and IL23p19-/- mice. Thirty-day mortality, hemodynamic function 4 days after MI and myocardial inflammation, and remodeling 4 and 30 days after MI were examined. Differentiation of fibroblasts from infarcted and noninfarcted hearts into myofibroblasts was examined under basal conditions and after stimulation with interferon-γ, IL-17α and IL-23. Interleukin-23p19-/- mice showed higher expression of proinflammatory cytokines and immune cell infiltration in the scar early after MI compared with wild-type mice. A stronger interferon-γ/Th1 reaction seemed to be responsible for the increased inflammation under IL-23 deficiency. Expression of α-smooth muscle actin (α-SMA), collagen I and III was significantly higher in the heart tissue and isolated cardiac fibroblasts 4 days after MI in the wild-type mice. Interleukin-23p19-/- mice showed impaired healing compared with wild-type mice, as seen by significantly higher mortality because of ventricular rupture (40% higher after 30 days) and stronger left ventricular dilation early after MI. Stimulation of cardiac fibroblasts with interferon-γ, the main Th1 cytokine, but not with IL-23 or IL-17α, led to a significant downregulation of α-smooth muscle actin, collagen I and III and decreased migration and differentiation to myofibroblasts.

Conclusions: IL-23 deficiency leads to increased myocardial inflammation and decreased cardiac fibroblast activation, associated with impaired scar formation and adverse remodeling after MI.

Keywords: fibroblasts; interleukin-23; left ventricular remodeling; myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Cicatrix / pathology
  • Cicatrix / physiopathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Fibroblasts / drug effects
  • Fibroblasts / pathology
  • Interferon-gamma / pharmacology
  • Interleukin-17 / pharmacology
  • Interleukin-23 / deficiency*
  • Interleukin-23 / pharmacology
  • Interleukin-23 / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardial Infarction / diagnosis*
  • Myocardial Infarction / mortality
  • Myocardial Infarction / physiopathology*
  • Prognosis
  • Wound Healing / physiology*


  • Cytokines
  • Interleukin-17
  • Interleukin-23
  • Interferon-gamma