Impaired healing of the skin is a notable cause of patient morbidity and 
mortality. In diabetic individuals, dysregulated inflammation contributes to 
delayed wound healing. Specific immunomodulatory agents may have a role in the 
treatment of diabetic wounds. One of these molecules is interleukin-1 receptor 
antagonist (Anakinra; Amgen Corp.). Although interleukin-1 receptor antagonist 
(Anakinra; Amgen Corp.) is approved by the Food and Drug Administration (FDA) 
for the treatment of rheumatoid arthritis and neonatal-onset multisystem 
inflammatory disease, little is known about the local use this drug in cutaneous 
wound healing. Therefore, the aim of this study is to determine the effect of 
locally administered interleukin-1 receptor antagonist on delayed wound healing, 
specifically, in a diabetic mouse model. Two 6-mm full-thickness wounds were 
created on the dorsa of diabetic (db/db) mice and stented. One-hour 
postwounding, wound margins were subcutaneously injected with either (1) 
low-dose interleukin-1 receptor antagonist in a gelatin-transglutaminase gel 
vehicle or (2) the gel vehicle only. Wounds were imaged on days 0, 7, 14, and 21 
postwounding, and wound area was determined. Wound biopsies were collected on 
day 21 and immunohistochemically stained for neutrophil and macrophage 
infiltration. Wounds treated with interleukin-1 receptor antagonist had 
significantly smaller wound area than nontreated wounds on day 7 and day 14 
postwounding. Treated wounds also showed significantly less neutrophil and 
macrophage infiltration. These findings support the hypothesis that 
interleukin-1 receptor antagonist may have an important role in cutaneous wound 
healing, possibly by promoting successful resolution of acute inflammation and 
hence accelerating wound closure. Thereby, administration of IL-1Ra may be 
useful in the treatment of nonhealing wounds.