Interleukin-10 reduces scar formation in both animal and human cutaneous wounds: Results of two preclinical and phase II randomized control studies
Interleukin-10 reduces scar formation in both animal and human cutaneous wounds: Results of two preclinical and phase II randomized control studies
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DOI：
10.1111/wrr.12043
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发表时间：
2013-05-01
影响因子：
2.9
通讯作者：
Ferguson, Mark
中科院分区：
文献类型：
--
作者：
Kieran, Ingrid;Knock, Amanda;Ferguson, Mark
皮肤瘢痕每年影响多达1亿人。迄今为止，还没有开发出有效的疤痕减少/预防治疗剂。白细胞介素（IL）-10是一种抗炎和抗纤维化的细胞因子。在胚胎中，它对无瘢痕伤口修复很重要。我们研究了在敲除（KO）小鼠模型中IL-10和IL-4基因的双缺失对伤口愈合和瘢痕形成的影响，以及外源性添加重组人（rh）IL-10到大鼠和人皮肤切口中的影响。小鼠研究：在20只双IL-4/IL-10 KO小鼠和20只野生型（WT）对照的背部皮肤上制作两个切口。大鼠研究：研究了三种浓度的rhIL-10。在30只大鼠背部皮肤上做4个切口。每只大鼠接受两种浓度。接受rhIL-10浓度的每个切口与接受安慰剂或标准护理的对照切口相匹配。人体研究：研究了8种浓度的rhIL-10。在175名健康志愿者的每只手臂上做四个切口。四个切口接受四种不同的浓度，与接受标准护理或安慰剂的四个对照切口相匹配。KO小鼠愈合后瘢痕组织学较差，炎症增加。rhIL-10治疗的大鼠切口愈合，炎症减少，瘢痕组织学更好，宏观瘢痕外观更好。低浓度rhIL-10处理的人切口愈合具有更好的宏观瘢痕外观和较少的红色瘢痕。IL-10是伤口愈合中的重要细胞因子，其对炎症和瘢痕形成的抑制在小鼠和大鼠中得到证实，在人中具有转化效应。
Cutaneous scarring affects up to 100million people per annum. There is no effective scar reducing/preventing therapeutic developed to date. Interleukin (IL)-10 is an anti-inflammatory and antifibrotic cytokine. In the embryo it is important for scarless wound repair. We investigated the effect on wound healing and scarring of a double deletion of the IL-10 and IL-4 genes in a knockout (KO) mouse model, and also the effect of exogenous addition of recombinant human (rh) IL-10 into rat and human cutaneous incisions. Mouse study: Two incisions were made on the dorsal skin of 20 double IL-4/IL-10 KO mice and 20 wild-type (WT) controls. Rat study: Three concentrations of rhIL-10 were investigated. Four incisions were made on the dorsal skin of 30 rats. Each rat received two concentrations. Each incision receiving a concentration of rhIL-10 was matched with a control incision, which received either placebo or standard care. Human study: Eight concentrations of rhIL-10 were investigated. Four incisions were made on each arm of 175 healthy volunteers. Four incisions received four different concentrations, which were matched with four control incisions that received either standard care or placebo. KO mice healed with poor scar histology and increased inflammation. rhIL-10treated rat incisions healed with decreased inflammation, better scar histology, and better macroscopic scar appearance. rhIL-10treated human incisions at low concentrations healed with better macroscopic scar appearance and less red scars. IL-10 is an important cytokine in wound healing and its suppression of inflammation and scarring is demonstrated in mice and rats with a translational effect in humans.