Institute of Pathology, University Hospital, Friedrich Schiller University, Jena, Germany.
Ann Rheum Dis. 2012 Feb;71(2):253-61. doi: 10.1136/ard.2011.150318. Epub 2011 Sep 27.
Both facilitatory and inhibitory effects of the sympathetic nervous system (SNS) on experimental arthritis have been reported. It is unknown whether such bidirectional effects are inherent to all experimental arthritis models and/or whether critical time windows exist for influences of the SNS on inflammation.
To assess the effect of sympathectomy at different time points on the course and severity of murine antigen-induced arthritis (AIA).
AIA was induced in mice. Chemical sympathectomy with 6-hydroxydopamine was carried out either neonatally, in the immunisation phase, or immediately before AIA elicitation, or during the chronic phase. In sympathectomised and non-sympathectomised AIA mice the inflammatory process (joint swelling, histopathology of inflammation and joint destruction), pain-related behaviour and cellular and humoral immune responses were analysed.
Sympathectomy during AIA induction or neonatal sympathectomy significantly reduced the severity of acute AIA. Neither sympathectomy in the immunisation phase nor in the chronic phase influenced AIA. Flare-up reactions were reduced by sympathectomy just before flare-up or during the initial acute AIA stage. Sympathectomised AIA mice showed less hyperalgesia. Sympathectomy significantly reduced interleukin (IL) 2, IL-17 and transforming growth factor β in supernatants from lymph nodes and/or spleen cells and antigen-specific Th1-associated IgG2a in serum; IgG1 titres were unaffected. The ß blocker, propranolol, and the norepinephrine reuptake inhibitor bupropion produced similar anti-inflammatory effects, whereas the ß-adrenergic agonist isoproterenol increased AIA severity in neonatally sympathectomised mice.
Sympathetic activity mainly increases the severity of acute episodes of immune-mediated arthritis. Therapeutic reduction of sympathetic activity at acute stages attenuates inflammation, hyperalgesia and proinflammatory immune parameters.
交感神经系统（SNS）对实验性关节炎既有促进作用，也有抑制作用。目前尚不清楚这种双向作用是否是所有实验性关节炎模型所固有的，以及 SNS 对炎症的影响是否存在关键的时间窗口。
评估不同时间点交感神经切除术对鼠抗原诱导关节炎（AIA）病程和严重程度的影响。
在小鼠中诱导 AIA。用 6-羟多巴胺进行化学性交感神经切除术，分别在新生儿期、免疫期或 AIA 诱发前、慢性期进行。在交感神经切除和非交感神经切除的 AIA 小鼠中，分析炎症过程（关节肿胀、炎症组织病理学和关节破坏）、痛觉相关行为以及细胞和体液免疫反应。
在 AIA 诱导时或新生儿期行交感神经切除术可显著减轻急性 AIA 的严重程度。免疫期或慢性期的交感神经切除术均不影响 AIA。在发作前或初始急性 AIA 阶段行交感神经切除术可减少发作反应。交感神经切除的 AIA 小鼠表现出较低的痛觉过敏。交感神经切除术显著降低了淋巴结和/或脾细胞上清液中的白细胞介素（IL）2、IL-17 和转化生长因子β以及血清中抗原特异性 Th1 相关 IgG2a；IgG1 滴度不受影响。β 阻滞剂普萘洛尔和去甲肾上腺素再摄取抑制剂丁丙诺啡产生类似的抗炎作用，而β-肾上腺素能激动剂异丙肾上腺素则会增加新生儿期交感神经切除小鼠的 AIA 严重程度。
交感神经活动主要增加免疫介导性关节炎急性发作的严重程度。在急性发作期减少交感神经活性可减轻炎症、痛觉过敏和促炎免疫参数。
