Granulocyte-macrophage colony-stimulating factor enhances wound healing in diabetes via upregulation of proinflammatory cytokines

Br J Dermatol. 2010 Mar;162(3):478-86. doi: 10.1111/j.1365-2133.2009.09528.x. Epub 2009 Oct 3.


Background: Chronic ulceration, especially in diabetes, remains a substantial clinical problem. Exogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) is efficacious in the treatment of chronic wound healing in both animal models and patients, but its role in diabetic wounds remains to be explored. Objectives Using a diabetic mouse model, to investigate the role of GM-CSF in wound healing.

Methods: Clinical observation, histopathology, immunohistochemistry and cytokine assays.

Results: There was a significant reduction (50%) in GM-CSF production in the wounds of the diabetics compared with nondiabetics. Exogenous GM-CSF substantially enhanced the wound healing in diabetic mice, accompanied by increased interleukin-6 and monocyte chemoattractant protein-1 production. The elevated cytokines correlated with increased neovascularization, and infiltration of macrophages and neutrophils. GM-CSF showed no beneficial effects in nondiabetic wound healing.

Conclusions: Our results provide useful guidelines for the clinical management of chronic ulceration in diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Chemokine CCL2 / biosynthesis
  • Collagen / metabolism
  • Colony-Stimulating Factors / metabolism*
  • Cytokines / metabolism*
  • Diabetes Mellitus, Experimental / metabolism*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Interleukin-6 / biosynthesis
  • Male
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Neovascularization, Physiologic / physiology
  • Up-Regulation / physiology*
  • Wound Healing / physiology*


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Colony-Stimulating Factors
  • Cytokines
  • Interleukin-6
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Collagen