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Increased Responsiveness of Peripheral Blood Mononuclear Cells to In Vitro TLR 2 4 and 7 Ligand Stimulation in Chronic Pain Patients

机译:在慢性疼痛患者中增加外周血单个核细胞的响应性在体外TLR 24和7配体刺激

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摘要

Glial activation via Toll-like receptor (TLR) signaling has been shown in animals to play an important role in the initiation and establishment of chronic pain. However, our ability to assess this central immune reactivity in clinical pain populations is currently lacking. Peripheral blood mononuclear cells (PBMCs) are an accessible source of TLR expressing cells that may mirror similarities in TLR responsiveness of the central nervous system. The aim of this study was to characterize the IL-1β response to various TLR agonists in isolated PBMCs from chronic pain sufferers (on and not on opioids) and pain-free controls. Venous blood was collected from 11 chronic pain sufferers on opioids (≥ 20 mg of morphine / day), 8 chronic pain sufferers not on opioids and 11 pain-free controls. PBMCs were isolated and stimulated in vitro with a TLR2 (Pam3CSK4), TLR4 (LPS) or TLR7 (imiquimod) agonist. IL-1β released into the supernatant was measured with ELISA. Significantly increased IL-1β expression was found in PBMCs from chronic pain sufferers (on and not on opioids) compared with pain-free controls for TLR2 (F (6, 277) = 15, P<0.0001), TLR4 (F (8, 263) = 3, P = 0.002) and TLR7 (F (2,201) = 5, P = 0.005) agonists. These data demonstrate that PBMCs from chronic pain sufferers were more responsive to TLR agonists compared with controls, suggesting peripheral cells may have the potential to become a source of biomarkers for chronic pain.
机译:在动物中,经由Toll样受体(TLR)信号传导进行的神经胶质激活在慢性疼痛的发生和建立中起着重要作用。但是,目前缺乏评估临床疼痛人群中这种中枢免疫反应性的能力。外周血单核细胞(PBMC)是TLR表达细胞的一种可获取来源,可能反映了中枢神经系统TLR反应性的相似性。这项研究的目的是鉴定来自慢性疼痛患者(阿片类药物和非阿片类药物)和无疼痛对照的分离的PBMC中对各种TLR激动剂的IL-1β反应。从11名使用阿片类药物(≥20 mg吗啡/天)的慢性疼痛患者,8名非阿片类药物慢性疼痛患者和11名无疼痛对照中收集静脉血。分离PBMC,并在体外用TLR2(Pam3CSK4),TLR4(LPS)或TLR7(咪喹莫特)激动剂刺激。用ELISA测定释放到上清液中的IL-1β。与无疼痛对照的TLR2(F(6,277)= 15,P <0.0001),TLR4(F(8,8)相比,在慢性疼痛患者的PBMC中(在阿片类药物上和非在阿片类药物上)发现IL-1β表达显着增加。 263)= 3,P = 0.002)和TLR7(F(2,201)= 5,P = 0.005)激动剂。这些数据表明,与对照组相比,来自慢性疼痛患者的PBMC对TLR激动剂的反应更强,这表明外周细胞可能具有成为慢性疼痛生物标志物来源的潜力。

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