A cascade of cytokines mediates mechanical inflammatory hypernociception in mice
A cascade of cytokines mediates mechanical inflammatory hypernociception in mice
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DOI：
10.1073/pnas.0409225102
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发表时间：
2005-02-01
影响因子：
11.1
通讯作者：
Ferreira, SH
中科院分区：
文献类型：
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作者：
Cunha, TM;Verri, WA;Ferreira, SH
研究了细胞因子[tnf - α，角化细胞来源的趋化因子（KC）和il -1 β]在卡拉胶（Cg）诱导的小鼠炎症性高痛觉中的作用及其参与。在WT和TNF受体1型敲除小鼠（TNF- r1(-/-)）中，用电子版本的von Frey纤维试验量化伤害感受器致敏（高痛觉）。tnf - α诱导的高痛觉在TNF-R1（-/-）小鼠中被消除，IL-1受体拮抗剂（IL-1ra）或吲哚美辛预处理部分抑制，抗KC （AbKC）或胍乙啶的Ab不影响。IL-1ra和吲哚美辛预处理强烈抑制il -1 β诱导的高痛觉，而AbKC、胍乙啶或敲除TNF-R1均不改变il -1 β诱导的高痛觉。AbKC可消除kc诱导的高痛觉，吲哚美辛加胍乙啶预处理可抑制kc诱导的高痛觉，IL-1ra、吲哚美辛或胍乙啶可部分抑制kc诱导的高痛觉。相反，敲除TNF-R1不会改变kc诱导的高痛觉性。用吲哚美辛加胍乙啶可消除cg诱导的高痛觉，在TNF-R-1（-/-）小鼠中减少，在用AbKC、IL-1ra、吲哚美辛或胍乙啶预处理的WT小鼠中部分抑制。注射cg的爪子皮肤中tnf - α、KC和il -1 β浓度升高。tnf - α和KC浓度同时升高，且在il -1 - β之前达到峰值。在小鼠中，细胞因子级联始于tnf - α（作用于TNF-R1受体）和KC的释放，它们刺激il -1 β的释放。在大鼠中，这个级联的最终介质是il -1 β释放的前列腺素和KC释放的交感胺。这些结果延伸到小鼠的概念，即负责高痛觉的主要介质的释放之前是一个细胞因子级联。
The hypernociceptive effects of cytokines [TNF-alpha, keratinocyte-derived chemokine (KC), and IL-1beta] and their participation in carrageenan (Cg)-induced inflammatory hypernociception in mice were investigated. Nociceptor sensitization (hypernociception) was quantified with an electronic version of the von Frey filament test in WT and TNF receptor type 1 knockout mice (TNF-R1(-/-)). TNF-alpha-incluced hypernociception was abolished in TNF-R1(-/-) mice, partially inhibited by pretreatment with IL-1 receptor antagonist (IL-1ra) or indomethacin and unaffected by Ab against KC (AbKC) or guanethidine. IL-1ra and indomethacin pretreatment strongly inhibited the hypernociception induced by IL-1beta, which was not altered by AbKC or guanethidine or by knocking out TNF-R1. KC-induced hypernociception was abolished by AbKC, inhibited by pretreatment with indomethacin plus guanethidine, and partially inhibited by IL-1ra, indomethacin, or guanethidine. In contrast, KC-induced hypernociception was not altered by knocking out TNF-R1. Cg-induced hypernociception was abolished by administration of indomethacin plus guanethidine, diminished in TNF-R-1(-/-) mice, and partially inhibited in WT mice pretreated with AbKC, IL-1ra, indomethacin, or guanethicline. TNF-alpha, KC, and IL-1beta concentrations were elevated in the skin of Cg-injected paws. The TNF-alpha and KC concentrations rose concomitantly and peaked before that of IL-1beta. In mice, the cytokine cascade begins with the release of TNF-alpha (acting on TNF-R1 receptor) and KC, which stimulate the release of IL-1beta. As in rats, the final mediators of this cascade were Prostaglandins released by IL-1beta and sympathetic amines released by KC. These results extend to mice the concept that the release of primary mediators responsible for hypernociception is preceded by a cascade of cytokines.