Center for Neurobiology of Stress, University of California, Los Angeles, California 90095-7378, USA.
Am J Gastroenterol. 2012 Feb;107(2):262-72. doi: 10.1038/ajg.2011.423. Epub 2011 Dec 13.
Low-grade colonic mucosal inflammation has been postulated to have an important role in the pathophysiology of irritable bowel syndrome (IBS). The objectives of this study were (i) to identify serum and tissue-based immunological and neuroendocrine markers associated with mucosal inflammation in male (M) and female (F) patients with non-post-infectious IBS (non-PI-IBS) compared with healthy controls and (ii) to assess possible correlations of such markers with IBS symptoms.
Sigmoid mucosal biopsies were obtained from 45 Rome II positive IBS patients without a history of PI-IBS (26 F, 35.5% IBS-C, 33.3% IBS-D, 31.1% IBS-A/M) and 41 healthy controls (22 F) in order to measure immunological markers (serum cytokine levels, colonic mucosal mRNA levels of cytokines, mucosal immune cell counts) and neuroendocrine markers associated with mucosal inflammation (corticotropin releasing factor- and neurokinin (NK)-related ligands and receptors, enterochromaffin cells). Symptoms were measured using validated questionnaires.
Of all the serum and mucosal cytokines measured, only interleukin-10 (IL-10) mRNA expression showed a group difference, with female, but not male, patients showing lower levels compared with female controls (18.0±2.9 vs. 29.5±4.0, P=0.006). Mucosal mRNA expression of NK-1 receptor was significantly lower (1.15±0.19 vs. 2.66±0.56, P=0.008) in female, but not male, patients compared with healthy controls. No other significant differences were observed.
Immune cell counts and levels of cytokines and neuropeptides that are associated with inflammation were not significantly elevated in the colonic mucosa of non-PI-IBS patients, and did not correlate with symptoms. Thus, these findings do not support that colonic mucosal inflammation consistently has a primary role in these patients. However, the finding of decreased IL-10 mRNA expression may be a possible biomarker of IBS and warrants further investigation.
低度结肠黏膜炎症被认为在肠易激综合征（IBS）的病理生理学中具有重要作用。本研究的目的是（i）确定与非感染后 IBS（非 PI-IBS）男性（M）和女性（F）患者的黏膜炎症相关的血清和组织免疫及神经内分泌标志物，并与健康对照进行比较；（ii）评估这些标志物与 IBS 症状的可能相关性。
从 45 名罗马 II 阳性的非 PI-IBS 肠易激综合征患者（26 名女性，35.5% IBS-C，33.3% IBS-D，31.1% IBS-A/M）和 41 名健康对照中获得乙状结肠黏膜活检组织，以测量免疫标志物（血清细胞因子水平、结肠黏膜细胞因子 mRNA 水平、黏膜免疫细胞计数）和与黏膜炎症相关的神经内分泌标志物（促肾上腺皮质释放因子和神经激肽（NK）相关配体和受体、肠嗜铬细胞）。使用经过验证的问卷来测量症状。
在所测量的所有血清和黏膜细胞因子中，只有白细胞介素 10（IL-10）mRNA 表达显示出组间差异，女性患者，而不是男性患者，与女性对照组相比，水平较低（18.0±2.9 vs. 29.5±4.0，P=0.006）。与健康对照组相比，女性而非男性患者的 NK-1 受体黏膜 mRNA 表达显著降低（1.15±0.19 vs. 2.66±0.56，P=0.008）。
非 PI-IBS 患者的结肠黏膜中，与炎症相关的免疫细胞计数以及细胞因子和神经肽水平并未显著升高，且与症状无相关性。因此，这些发现并不支持结肠黏膜炎症在这些患者中始终具有主要作用。然而，IL-10 mRNA 表达降低的发现可能是 IBS 的一个潜在生物标志物，值得进一步研究。
