Local Administration of Interleukin-1 Receptor Antagonist Improves Diabetic Wound Healing.
Local Administration of Interleukin-1 Receptor Antagonist Improves Diabetic Wound Healing.
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DOI：
10.1097/sap.0000000000001417
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发表时间：
2018-05
影响因子：
1.5
通讯作者：
Wong AK
中科院分区：
文献类型：
--
作者：
Perrault DP;Bramos A;Xu X;Shi S;Wong AK
皮肤愈合不良是患者发病率和死亡率的显著原因。在糖尿病患者中，炎症失调导致伤口愈合延迟。特定的免疫调节剂可能在糖尿病伤口的治疗中发挥作用。这些分子之一是白细胞介素-1受体拮抗剂（Anakinra; Amgen Corp.）。虽然白细胞介素-1受体拮抗剂（阿那白滞素;安进公司）美国食品和药物管理局（FDA）批准该药用于治疗类风湿性关节炎和脑源性多系统炎性疾病，但对该药在皮肤伤口愈合中的局部应用知之甚少。因此，本研究的目的是确定局部施用白细胞介素-1受体拮抗剂对延迟伤口愈合的影响，特别是在糖尿病小鼠模型中。在糖尿病（db/db）小鼠的背上产生两个6-mm全厚度伤口并植入支架。伤后1小时，伤口边缘皮下注射（1）明胶-转氨酶凝胶载体中的低剂量白细胞介素-1受体拮抗剂或（2）仅凝胶载体。在伤后第0、7、14和21天对伤口进行成像，并确定伤口面积。在第21天收集伤口活组织检查，并对中性粒细胞和巨噬细胞浸润进行化学染色。在伤后第7天和第14天，用白细胞介素-1受体拮抗剂治疗的伤口比未治疗的伤口具有显著更小的伤口面积。经治疗的伤口还显示出显著较少的嗜中性粒细胞和巨噬细胞浸润。这些发现支持了白细胞介素-1受体拮抗剂可能在皮肤伤口愈合中发挥重要作用的假设，可能是通过促进急性炎症的成功消退，从而加速伤口闭合。因此，IL-1 Ra的施用可用于治疗不愈合的伤口。
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.