Use of rhGM-CSF promotes wound healing via macrophage immunomodulation

Topical administration of recombinant human granulocyte macrophage–colony stimulating factor (rhGM-CSF) helps induce healing of diabetic and nondiabetic wounds, suggests a study.

To validate the effect and molecular mechanisms of rhGM-CSF, two full-thickness wounds were made on the backs of C57BL/6J mice. The caudal wounds were treated with topical rhGM-CSF (1.0 μg/cm²) daily, while the cranial wounds were treated with saline. Patients with diabetic lower extremity ulcers were also randomly assigned to the rhGM-CSF intervention (2.0 μg/cm² infiltration) and control groups.

The overall percentage area reduction by 1 month served as the primary endpoint. Wound tissues were stained with hematoxylin and eosin and immunofluorescence. The authors then analysed macrophage subtypes by performing Western blots.

In C57BL/6J mice, topical use of rhGM-CSF significantly accelerated wound healing (average healing rate, 2.53 mm²/day). The study drug also resulted in an increase in the capillary marker CD31 and the expression of vascular endothelial growth factor A.

In the clinical trial, 48 participants with similar baseline characteristics were randomized into rhGM-CSF (n=27) or control (n=21) groups. The rhGM-CSF group demonstrated greater overall percentage area reduction (97.7 percent) than did the control group (p<0.05).

Topical administration with rhGM-CSF significantly reduced M1-type macrophages and increased M2-type macrophages, with M2a predominating at day 5 and M2d dominating at day 10 following injury.

“Our study suggested that topical administration of rhGM-CSF can promote the healing of both diabetic and nondiabetic wounds, which is partly attributable to promoting the transformation of macrophages to M2 subtype,” the authors said.