Granulocyte-colony stimulating factor (G-CSF)-induced mechanical hyperalgesia in mice: Role for peripheral TNFα, IL-1β and IL-10
Granulocyte-colony stimulating factor (G-CSF)-induced mechanical hyperalgesia in mice: Role for peripheral TNFα, IL-1β and IL-10
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DOI：
10.1016/j.ejphar.2014.12.023
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发表时间：
2015-02-15
影响因子：
5
通讯作者：
Verri, Waldiceu A., Jr.
中科院分区：
文献类型：
--
作者：
Carvalho, Thacyana T.;Borghi, Sergio M.;Verri, Waldiceu A., Jr.
粒细胞集落刺激因子（G-CSF）是一种在抗肿瘤治疗后增加外周中性粒细胞计数的治疗方法。疼痛是 G-CSF 的主要副作用 在小鼠体内给予 G-CSF 会引起机械性痛觉过敏。然而，参与这种效应的外围机制尚未阐明。因此，研究了促伤害细胞因子肿瘤坏死因子（TNF）α（TNF α）、白细胞介素（IL）-1β（IL-1β）和抗伤害细胞因子IL-10在G-CSF诱导的小鼠机械性痛觉过敏中的参与。 G-CSF诱导的机械痛觉过敏可通过依那西普和IL-1受体拮抗剂（IL-1ra）或TNF受体1（TNFR1）缺陷的全身和局部治疗得到抑制，并且在IL-10缺陷小鼠中增加。一致认为，G-CSF 注射诱导爪组织中显着产生 TNF α、IL-1 β 3 和 IL 10。 G-CSF 诱导的痛觉过敏受到沙利度胺 (5-45 mg/kg) 和己酮可可碱 (0.5-13.5 mg/kg) 的剂量依赖性抑制，并且用这些药物治疗可抑制 G-CSF 诱导的 TNF α、IL-1 β 和 IL 10 的产生。己酮可可碱或沙利度胺与吗啡的联合治疗，在单一治疗无效的剂量下，通过抑制细胞因子的产生来减少 G-CSF 诱导的痛觉过敏。单独使用吲哚美辛或与己酮可可碱或沙利度胺联合使用还可减少 G-CSF 痛觉过敏。因此，G-CSF 诱导的痛觉过敏可能是由外周产生的促伤害性细胞因子 TNF α 和 IL1 β 介导的，并被 IL 10 下调，全身性 IL-1ra 减少了 G-CSF 诱导的外周中性粒细胞计数的增加。然而，吗啡、IL-1ra或依那西普的局部治疗以及吲哚美辛、依那西普、沙利度胺和己酮可可碱的全身治疗并没有改变G-CSF诱导的中性粒细胞动员。因此，本研究推进了对 G-CSF 诱导的痛觉过敏的理解，并提出了控制其的治疗方法。 （三）。 2015 Elsevier B.V. 保留所有权利。
Granulocyte-colony stimulating factor (G-CSF) is a therapeutic approach to increase peripheral neutrophil counts after anti-tumor therapies. Pain is the major side effect of G-CSF Intraplantar administration of G-CSF in mice induces mechanical hyperalgesia. However, the peripheral mechanisms involved in this effect were not elucidated. Therefore, the participation of pronociceptive cytokines tumor necrosis factor (TNF) alpha (TNF alpha), interleukin (IL)-1 beta (IL-1 beta) and antinociceptive cytokine IL-10 in G-CSF-induced mechanical hyperalgesia in mice was investigated. G-CSF-induced mechanical hyperalgesia was inhibited by systemic and local treatment with etanercept and IL-1 receptor antagonist (IL-1ra) or TNF receptor 1 (TNFR1) deficiency and increased in IL-10 deficient mice. In agreement, G-CSF injection induced significant TNF alpha, IL-1 beta 3 and IL 10 production in paw tissue. G-CSF-induced hyperalgesia was dose dependently inhibited by thalidomide (5-45 mg/kg) and pentoxifylline (0.5-13.5 mg/kg), and treatment with these drugs inhibited G-CSF-induced TNF alpha, IL-1 beta and IL 10 production. The combined treatment with pentoxifylline or thalidomide with morphine, at doses that are ineffective as single treatment, diminished G-CSF-induced hyperalgesia through inhibiting cytokine production. Indomethacin also reduces G-CSF hyperalgesia alone or combined with pentoxifylline or thalidomide. Thus, G-CSF-induced hyperalgesia might be mediate by peripheral production of pronociceptive cyrokines TNF alpha and IL1 beta and down regulated by IL 10, Systemic IL-1ra reduced G-CSF-induced increase of peripheral neutrophil counts. However, local treatment with morphine, IL-1ra or etanercept, and systemic treatment with indomethacin, etanercept, thalidomide and pentoxifylline did not alter G-CSF-induced mobilization of neutrophils. Therefore, this study advances in the understanding of G-CSF-induced hyperalgesia and suggests therapeutic approaches for its control. (C). 2015 Elsevier B.V. All rights reserved.