Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome
Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome
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DOI：
10.1038/ajg.2016.223
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发表时间：
2016-08-01
影响因子：
9.8
通讯作者：
Ohman, Lena
中科院分区：
文献类型：
--
作者：
Bennet, Sean M. P.;Polster, Annikka;Ohman, Lena
目的：有证据表明，肠易激综合征（IBS）患者的细胞因子谱发生了改变，尽管尚不清楚细胞因子是否与症状严重程度有关。我们的目的是确定IBS患者和健康受试者的血清和粘膜细胞因子谱是否存在差异，以及细胞因子是否与IBS症状相关。分析来自144名IBS患者和42名健康受试者的血清的白细胞介素（IL）-5、IL-6、IL-8、IL-10、IL-12 p70、IL-13、IL-17 A、IL-17 B、IL-17 C、IL-18 C、IL-19 D、IL-19 C、IL-19干扰素（IFN）-γ和肿瘤坏死因子（TNF）。通过定量逆转录PCR分析了109例IBS和36例健康乙状结肠活检组织中IL-8、IL-10、TNF和FOXP 3的mRNA表达。多变量判别分析评价了总体细胞因子谱。直肠敏感性，oroanal传输时间，和心理和胃肠道症状的严重程度进行了assessed.RESULTS：IBS患者和健康受试者的全球细胞因子谱重叠，但细胞因子水平变化更IBS患者。IBS患者血清IL-6和IL-8水平有升高趋势，IFN-γ水平有降低趋势。IL-10和FOXP 3在IBS患者中的表达呈下降趋势。在整个研究队列和单独的IBS患者中，血清TNF水平与稀便模式相关，而具有更广泛躯体症状的受试者血清IL-6水平升高。虽然肠易激综合征肠道习惯亚组和可能感染后肠易激综合征患者均与不同的细胞因子谱相关，但确定了一小群免疫标志物相对升高的肠易激综合征患者。总体细胞因子谱不能区分IBS患者和健康受试者，但IBS患者的细胞因子谱比健康受试者的细胞因子谱变化更大，并且鉴定了具有增强的免疫活性的一小组患者。此外，炎性细胞因子与一些临床症状的关联表明免疫激活在IBS患者的子集中可能是重要的。
OBJECTIVES: Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms.METHODS: Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-gamma and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed.RESULTS: Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-gamma tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified.CONCLUSIONS: Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients.