Granulocyte-macrophage colony-stimulating factor enhances wound healing in diabetes via upregulation of proinflammatory cytokines.
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.
Department of Plastic Surgery, School of Medicine, Shanghai Third People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Y
Y
Fang
J
J
Shen
M
M
Yao
K W
KW
Beagley
B D
BD
Hambly
S
S
Bao
D000704:Analysis of Variance; D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D003094:Collagen / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D003115:Colony-Stimulating Factors; D016207:Cytokines; D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003094:Collagen