Wijaya Linda K, Stumbles Philip A, Finch Philip M, Drummond Peter D
School of Psychology, College of Health and Education, Murdoch University, 90 South St, Perth, Western Australia 6150, Australia; Telethon Kids Institute, Perth Children Hospital, 15 Hospital Avenue, Perth, Western Australia 6009, Australia.
School of Psychology, College of Health and Education, Murdoch University, 90 South St, Perth, Western Australia 6150, Australia.
Brain Behav Immun. 2024 Jan;115:201-208. doi: 10.1016/j.bbi.2023.10.015. Epub 2023 Oct 15.
Persistent regional and systemic inflammation may promote pain and hyperalgesia in complex regional pain syndrome (CRPS). In this study, we investigated whether stimulation of α-adrenoceptors (α-AR) on peripheral blood mononuclear cells (PBMC) might contribute to this inflammatory state. PBMC were isolated from venous blood collected from 21 CRPS patients and 21 sex and age-matched controls. Lipopolysaccharide (LPS), a bacterial toxin, was administered to cultured PBMC for 24 h to trigger inflammation. Exposure to LPS resulted in heightened gene expression of α-AR subtype B (α-AR) in PBMC of CRPS patients relative to controls. Interleukin (IL)-1β and IL-6 levels did not change when the α-AR agonist phenylephrine was administered to naïve PBMC. However, α-AR stimulation following LPS treatment increased IL-6 mRNA and protein levels in PBMC of patients and controls. To investigate the possible consequence of heightened IL-6 levels on immunoglobulin G antibody production, PBMC were stimulated with CD40 ligand and IL-21 to generate plasmablasts (B cells that secrete antibodies). This response was similar in patients and controls. Adding IL-6 to the cell culture medium increased plasmablast differentiation in controls and antibody production both in patients and controls. These findings suggest that the inflammatory cascade associated with elevated levels of IL-6 may generate α-AR expression in CRPS PBMC. A reciprocal interaction between heightened α-AR expression in PBMC and IL-6 secretion may contribute to systemic inflammation and antibody production in CRPS.
持续性局部和全身炎症可能会促进复杂性区域疼痛综合征（CRPS）中的疼痛和痛觉过敏。在本研究中，我们调查了刺激外周血单核细胞（PBMC）上的α-肾上腺素能受体（α-AR）是否可能导致这种炎症状态。从21例CRPS患者以及21例年龄和性别匹配的对照者采集的静脉血中分离出PBMC。将细菌毒素脂多糖（LPS）加入培养的PBMC中24小时以引发炎症。与对照组相比，暴露于LPS导致CRPS患者PBMC中α-AR亚型B（α-AR）的基因表达升高。当将α-AR激动剂去氧肾上腺素给予未经处理的PBMC时，白细胞介素（IL）-1β和IL-6水平没有变化。然而，LPS处理后的α-AR刺激增加了患者和对照组PBMC中IL-6的mRNA和蛋白质水平。为了研究IL-6水平升高对免疫球蛋白G抗体产生的可能影响，用CD40配体和IL-21刺激PBMC以产生浆母细胞（分泌抗体的B细胞）。患者和对照组的这种反应相似。向细胞培养基中添加IL-6可增加对照组中的浆母细胞分化以及患者和对照组中的抗体产生。这些发现表明，与IL-6水平升高相关的炎症级联反应可能在CRPS的PBMC中产生α-AR表达。PBMC中α-AR表达升高与IL-6分泌之间的相互作用可能导致CRPS中的全身炎症和抗体产生。
