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.
Fang
Y
Y
Department of Plastic Surgery, School of Medicine, Shanghai Third People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Shen
J
J
Yao
M
M
Beagley
K W
KW
Hambly
B D
BD
Bao
S
S
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