The cytokine milieu of diabetic wounds

Nonhealing diabetic foot ulcers are a significant complication of diabetes. They develop due to peripheral neuropathy, and may take weeks or months to close. A failure to heal may necessitate lower limb amputation causing significant morbidity and mortality. Wound healing impairment in diabetic patients is associated with delays in immune cell migration and altered macrophage activation. These processes are orchestrated by the cytokine milieu in the wound manifested by an upregulation of proinflammatory cytokines and downregulation of anti-inflammatory cytokines. This review examines the current knowledge of cytokine expression (IL-1β, IL-6, IL-10, TNF-α, TGF-β, and C-reactive proteins as well as the chemokines CCL2 and CXCL12) and explores potential cytokine immunotherapy to aid healing.