The Role of Interleukin-1 in Wound Biology. Part II: In Vivo and Human Translational Studies
The Role of Interleukin-1 in Wound Biology. Part II: In Vivo and Human Translational Studies
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DOI：
10.1213/ane.0b013e3181f691eb
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发表时间：
2010-12-01
影响因子：
5.7
通讯作者：
Peltz, Gary
中科院分区：
文献类型：
--
作者：
Hu, Yajing;Liang, Deyong;Peltz, Gary
背景：在随附的论文中，我们证明 Nalp1 内的遗传变异可能通过改变白细胞介素 (IL)-1 的产生量，导致伤口趋化因子产生的种间差异。我们进一步研究了 IL-1 在切口伤口生物学中的作用及其对体内伤口趋化因子产生的影响，以及该机制是否可以在人类受试者中发挥作用。 方法：使用良好表征的小鼠切口伤口模型来评估 IL-1 在伤口生物学中的体内作用。在用 IL-1 抑制剂治疗的小鼠中，分析了实验诱导的小鼠爪子皮肤切口内产生的 7 种不同细胞因子/趋化因子的量以及伤害性反应。我们还研究了人 IL-1 β 或 IL-1 α 在体外是否刺激原代人角质形成细胞产生趋化因子，以及在 2 个实验人类伤口范例中 IL-1 β 和趋化因子水平之间是否存在相关性。 结果：给小鼠施用 IL-1 受体拮抗剂可降低对切口伤口的伤害性反应，并减少多种炎症介质的产生，包括角质形成细胞衍生的趋化因子 (KC) 和伤口内的巨噬细胞抑制蛋白（MIP）-1 α。 IL-1 α 和 IL-1 β 刺激原代人角质形成细胞在体外产生 IL-8 和 GRO-α（鼠角质形成细胞衍生趋化因子的人类同源物）。在人类手术伤口和人类紫外线 B 引起的晒伤损伤的皮肤部位，IL-1β 水平与 IL-8 高度相关。 结论：IL-1 通过一种新机制在调节伤口炎症介质产生中发挥重要作用。通过刺激多种细胞因子和趋化因子的产生，它影响伤口生物学的临床重要方面。这些数据表明，围手术期使用 IL-1 受体拮抗剂可以减轻术后伤口疼痛。
BACKGROUND: In the accompanying paper, we demonstrate that genetic variation within Nalp1 could contribute to interstrain differences in wound chemokine production through altering the amount of interleukin (IL)-1 produced. We further investigate the role of IL-1 in incisional wound biology and its effect on wound chemokine production in vivo and whether this mechanism could be active in human subjects.METHODS: A well-characterized murine model of incisional wounding was used to assess the in vivo role of IL-1 in wound biology. The amount of 7 different cytokines/chemokines produced within an experimentally induced skin incision on a mouse paw and the nociceptive response was analyzed in mice treated with an IL-1 inhibitor. We also investigated whether human IL-1 beta or IL-1 alpha stimulated the production of chemokines by primary human keratinocytes in vitro, and whether there was a correlation between IL-1 beta and chemokine levels in 2 experimental human wound paradigms.RESULTS: Administration of an IL-1 receptor antagonist to mice decreased the nociceptive response to an incisional wound, and reduced the production of multiple inflammatory mediators, including keratinocyte-derived chemokine (KC) and macrophage inhibitory protein (MIP)-1 alpha, within the wounds. IL-1 alpha and IL-1 beta stimulated IL-8 and GRO-alpha (human homologues of murine keratinocyte-derived chemokine) production by primary human keratinocytes in vitro. IL-1 beta levels were highly correlated with IL-8 in human surgical wounds, and at cutaneous sites of human ultraviolet B-induced sunburn injury.CONCLUSIONS: IL-1 plays a major role in regulating inflammatory mediator production in wounds through a novel mechanism; by stimulating the production of multiple cytokines and chemokines, it impacts clinically important aspects of wound biology. These data suggest that administration of an IL-1 receptor antagonist within the perioperative period could decrease postsurgical wound pain.