Lucas A, Cobelens P M, Kavelaars A, Heijnen C J, Holtmann G, Haag S, Gerken G, Langhorst J, Dobos G J, Schedlowski M, Elsenbruch S
Department of Medical Psychology, University Hospital of Essen Medical School, University of Duisburg-Essen, Germany.
J Neuroimmunol. 2007 Jan;182(1-2):195-203. doi: 10.1016/j.jneuroim.2006.09.011. Epub 2006 Nov 15.
Psychological stress has been implicated in the pathophysiology of both inflammatory and functional gastrointestinal (GI) diseases. The goal of this study was to address neuroendocrine modulation of cytokine production by peripheral blood cells in GI diseases.
We analyzed the in vitro effects of the beta-adrenergic agonist terbutaline and the glucocorticoid agonist dexamethasone on TNF-alpha and IL-10 production by LPS-stimulated monocytes in whole cell blood cultures in patients with inflammatory bowel diseases in remission (N=10), diarrhoea-predominant irritable bowel syndrome (IBS, N=12), patients with a recent gastroenteritis (post-infectious group, N=10), and healthy controls (N=15).
In response to terbutaline, there was a significant increase in IL-10 production (concentration effect: p<0.05), which was diminished in IBD (group effect: p<0.01), comparable in IBS and controls, but enhanced in the post-infectious group (group x concentration effect: p<0.05). In contrast, terbutaline resulted in a concentration-dependent suppression of TNF-alpha production, which was comparable in all groups. Dexamethasone suppressed TNF-alpha production in a dose-dependent manner in all groups, but this effect was significantly more pronounced in post-infectious subjects (group effect: p<0.05).
In IBD, disturbed adrenergic regulation of IL-10 could be part of the mechanism(s) underlying the modulation of disease activity by psychological stress. Diarrhoea-predominant IBS was not associated with altered adrenergic or glucocorticoid regulation of cytokine production by peripheral blood cells, whereas a recent history of gastroenteritis was associated with disturbed neuroendocrine modulation of cytokine production, which may play role in the pathophysiology of post-infectious IBS.
心理应激与炎症性和功能性胃肠（GI）疾病的病理生理学均有关联。本研究的目的是探讨胃肠疾病中外周血细胞产生细胞因子的神经内分泌调节。
我们分析了β-肾上腺素能激动剂特布他林和糖皮质激素激动剂地塞米松对处于缓解期的炎症性肠病患者（N = 10）、腹泻型肠易激综合征（IBS，N = 12）、近期患肠胃炎的患者（感染后组，N = 10）以及健康对照者（N = 15）全血细胞培养中经脂多糖刺激的单核细胞产生肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）的体外影响。
对特布他林的反应中，IL-10产生显著增加（浓度效应：p<0.05），在炎症性肠病中这种增加减弱（组效应：p<0.01），在肠易激综合征和对照组中相当，但在感染后组中增强（组×浓度效应：p<0.05）。相反，特布他林导致TNF-α产生呈浓度依赖性抑制，在所有组中相当。地塞米松在所有组中均以剂量依赖性方式抑制TNF-α产生，但这种效应在感染后受试者中明显更显著（组效应：p<0.05）。
在炎症性肠病中，IL-10的肾上腺素能调节紊乱可能是心理应激调节疾病活动的潜在机制的一部分。腹泻型肠易激综合征与外周血细胞产生细胞因子的肾上腺素能或糖皮质激素调节改变无关，而近期肠胃炎病史与细胞因子产生的神经内分泌调节紊乱有关，这可能在感染后肠易激综合征的病理生理学中起作用。
