Systemic translation of locally infiltrated epidermal growth factor in diabetic lower extremity wounds

Int Wound J. 2019 Dec;16(6):1294-1303. doi: 10.1111/iwj.13189. Epub 2019 Aug 19.

Abstract

Diabetic foot ulcer is one of the most frightened diabetic complications leading to amputation disability and early mortality. Diabetic wounds exhibit a complex networking of inflammatory cytokines, local proteases, and reactive oxygen and nitrogen species as a pathogenic polymicrobial biofilm, overall contributing to wound chronification and host homeostasis imbalance. Intralesional infiltration of epidermal growth factor (EGF) has emerged as a therapeutic alternative to diabetic wound healing, reaching responsive cells while avoiding the deleterious effect of proteases and the biofilm on the wound's surface. The present study shows that intralesional therapy with EGF is associated with the systemic attenuation of pro-inflammatory markers along with redox balance recovery. A total of 11 diabetic patients with neuropathic foot ulcers were studied before and 3 weeks after starting EGF treatment. Evaluations comprised plasma levels of pro-inflammatory, redox balance, and glycation markers. Pro-inflammatory markers such as erythrosedimentation rate, C-reactive protein, interleukin-6, soluble FAS, and macrophage inflammatory protein 1-alpha were significantly reduced by EGF therapy. Oxidative capacity, nitrite/nitrate ratio, and pentosidine were also reduced, while soluble receptor for advanced glycation end-products significantly increased. Overall, our results indicate that the local intralesional infiltration of EGF translates in systemic anti-inflammatory and antioxidant effects, as in attenuation of the glycation products' negative effects.

Keywords: diabetes; diabetic foot ulcer; epidermal growth factor; inflammation; oxidative stress.

MeSH terms

  • Aged
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Biomarkers / blood
  • Blood Sedimentation
  • C-Reactive Protein / analysis
  • Chemokine CCL3 / blood
  • Cytokines / blood
  • Diabetic Foot / drug therapy*
  • Epidermal Growth Factor / therapeutic use*
  • Female
  • Humans
  • Injections, Intralesional
  • Lysine / analogs & derivatives
  • Lysine / blood
  • Male
  • Middle Aged
  • Nitrates / blood
  • Nitrites / blood
  • Receptor for Advanced Glycation End Products / blood
  • Recombinant Proteins / therapeutic use*
  • Wound Healing
  • fas Receptor / blood

Substances

  • Biomarkers
  • Chemokine CCL3
  • Cytokines
  • Nitrates
  • Nitrites
  • Receptor for Advanced Glycation End Products
  • Recombinant Proteins
  • fas Receptor
  • Epidermal Growth Factor
  • C-Reactive Protein
  • Arginine
  • pentosidine
  • Lysine