Blockade of the complement C5a receptor reduces incisional allodynia, edema, and cytokine expression
Blockade of the complement C5a receptor reduces incisional allodynia, edema, and cytokine expression
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DOI：
10.1097/00000542-200606000-00024
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发表时间：
2006-06-01
期刊：
影响因子：
8.8
通讯作者：
Yeomans, David C.
中科院分区：
文献类型：
--
作者：
Clark, J. David;Qiao, Yanli;Yeomans, David C.
背景：补体系统的激活是炎症反应的一个组成部分。补体系统的各种组分参与杀死外来生物体、募集免疫细胞、增强水肿和刺激细胞因子形成。补体介导的增强手术切口周围的炎症可能会增加pains.Methods：在这些研究中，作者使用小鼠后爪切口模型来研究补体C5 a受体在支持切口炎症中的作用。在基线和切口后的不同时间点，他们测量了高度选择性C5 a受体拮抗剂对切口周围皮肤中伤害性阈值、水肿形成和细胞因子产生的影响。他们还测量了切口附近C5 a受体表达的变化。结果：每天一次注射C5 a受体拮抗剂AcF-[OPdChaWR]减少了切开后爪的机械异常性疼痛和水肿。多重细胞因子测定显示，所检查的18种细胞因子中的8种在切口后显示皮肤组织丰度显著增加。观察到升高模式的不同时间过程，尽管所有细胞因子在96小时内都出现了一定程度的消退。对于这8种细胞因子中的7种，C5 a受体拮抗剂降低了表达的增强。此外，作者发现，C5 a受体信使RNA水平增加了15倍，在皮肤周围的切口在24小时内，然后慢慢declined.Conclusions：组织直接周围的切口在小鼠后爪经历了很大的变化，在特定的细胞因子的含量，除了表现出水肿和伤害性敏化。通过阻断补体系统的一种成分C5 a的受体，所有这些变化都可以减少。补体受体抑制剂可能构成一组新的化合物，可用于减轻手术切口的疼痛和肿胀。
Background: Activation of the complement system is one component of the inflammatory response. Various components of the complement system participate in killing foreign organisms, recruiting immune cells, enhancing edema, and stimulating cytokine formation. Complement-mediated enhancement of the inflammation surrounding surgical incisions may increase pain.Methods: In these studies, the authors used a murine hind paw incisional model to study the role of the complement C5a receptor in supporting incisional inflammation. At baseline and at various time points after incision, they measured the effects of a highly selective C5a receptor antagonist on nociceptive thresholds, edema formation, and cytokine production in the skin surrounding the incision. They also measured changes in C5a receptor expression near the incisions.Results: The once-daily injection of the C5a receptor antagonist AcF-[OPdChaWR] reduced mechanical allodynia and edema in the incised hind paw. A multiplexed cytokine assay revealed that 8 of the 18 cytokines examined showed significant increases in skin tissue abundance after incision. Distinct time courses for the patterns of elevation were seen, though some degree of resolution occurred for all cytokines within 96 h. For 7 of these 8 cytokines, the C5a receptor antagonist reduced the enhancement of expression. in addition, the authors found that the C5a receptor messenger RNA level increased 15-fold in the skin surrounding the incisions within 24 h and then slowly declined.Conclusions: The tissue directly surrounding incisions in mouse hind paws undergoes large changes in the content of specific cytokines in addition to demonstrating edema and nociceptive sensitization. By blocking the receptor for one component of the complement system, C5a, all of these changes can be reduced. Complement receptor inhibitors may constitute a novel group of compounds useful in reducing the pain and swelling of surgical incisions.