Sensory neuro-immune interactions differ between Irritable Bowel Syndrome subtypes
Sensory neuro-immune interactions differ between Irritable Bowel Syndrome subtypes
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DOI：
10.1136/gutjnl-2011-301856
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发表时间：
2013-10-01
期刊：
影响因子：
24.5
通讯作者：
Brierley, Stuart M.
中科院分区：
文献类型：
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作者：
Hughes, Patrick A.;Harrington, Andrea M.;Brierley, Stuart M.
目的肠道是免疫系统和感觉系统的主要接触部位，肠易激综合征（IBS）患者存在免疫功能紊乱。在这里，我们展示了这种功能障碍之间的主要IBS亚群和免疫细胞如何与感觉nerves.Design沟通的不同，从20腹泻为主的IBS（D-IBS）患者，15便秘为主的IBS（C-IBS）患者和36名健康受试者的外周血单核细胞上清液被施加到小鼠结肠感觉神经和机械敏感性评估的影响。通过蛋白质组学分析评估上清液中的细胞因子/趋化因子浓度，并将其与腹部症状相关联，并在结肠背根神经节神经元中评估细胞因子受体的表达。结果D-IBS培养上清引起小鼠结肠传入末梢的机械性超敏反应，英夫利昔单抗可降低D-IBS培养上清引起的机械性超敏反应。C-IBS上清液没有，但偶尔升高基础放电。健康受试者的上清液抑制传入机械敏感性通过阿片类药物的机制。IBS上清液中的几种细胞因子升高，并且水平与患者的疼痛频率和强度相关。内脏传入纤维表达IL-1、IL-6、IL-10和TNF-α受体。TNF-α最有效地引起机械超敏反应，其被瞬时受体电位通道TRPA 1拮抗剂阻断。IL-1升高的基础射击，这是失去河豚毒素阻断钠通道后，结论不同的模式的免疫功能障碍和相互作用与感觉通路发生在不同的患者群体，并通过不同的细胞内途径。我们的研究结果表明，IBS患者亚组将受益于免疫系统的选择性靶向。
Objective The gut is a major site of contact between immune and sensory systems and evidence suggests that patients with irritable bowel syndrome (IBS) have immune dysfunction. Here we show how this dysfunction differs between major IBS subgroups and how immunocytes communicate with sensory nerves.Design Peripheral blood mononuclear cell supernatants from 20 diarrhoea predominant IBS (D-IBS) patients, 15 constipation predominant IBS (C-IBS) patients and 36 healthy subjects were applied to mouse colonic sensory nerves and effects on mechanosensitivity assessed. Cytokine/chemokine concentration in the supernatants was assessed by proteomic analysis and correlated with abdominal symptoms, and expression of cytokine receptors evaluated in colonic dorsal root ganglia neurons. We then determined the effects of specific cytokines on colonic afferents.Results D-IBS supernatants caused mechanical hypersensitivity of mouse colonic afferent endings, which was reduced by infliximab. C-IBS supernatants did not, but occasionally elevated basal discharge. Supernatants of healthy subjects inhibited afferent mechanosensitivity via an opioidergic mechanism. Several cytokines were elevated in IBS supernatants, and levels correlated with pain frequency and intensity in patients. Visceral afferents expressed receptors for four cytokines: IL-1, IL-6, IL-10 and TNF-. TNF- most effectively caused mechanical hypersensitivity which was blocked by a transient receptor potential channel TRPA1 antagonist. IL-1 elevated basal firing, and this was lost after tetrodotoxin blockade of sodium channels.Conclusions Distinct patterns of immune dysfunction and interaction with sensory pathways occur in different patient groups and through different intracellular pathways. Our results indicate IBS patient subgroups would benefit from selective targeting of the immune system.