Immunomodulatory cytokines suppress epithelial nitric oxide production in inflammatory bowel disease by acting on mononuclear cells

Inducible nitric oxide synthase (iNOS) activity in colonic epithelial HT-29 cells is modulated by the T-cell-derived cytokines IL-4 and IL-13, but is not affected by IL-10 despite its effect in models of colitis. We studied the effects of these cytokines on nitric oxide (NO) production by colonic tissue. IL-10 and IL-4 but not IL-13 suppressed the NO production and iNOS expression by inflamed tissue and cytokine-stimulated noninflamed tissue from patients with ulcerative colitis, whereas the three cytokines suppressed NO production in cytokine-stimulated biopsies from controls. To examine why colonic biopsies and HT-29 cells respond differently to immunomodulatory cytokines, a coculture of mixed mononuclear monocytes (MMC) and HT-29 cells was studied. Treatment of HT-29 cells with conditioned medium from IFN-γ/LPS-stimulated MMC produced significant amounts of NO, which suggested the presence of an MMC-derived soluble factor modifying epithelial NO production. Pretreatment of IFN-γ/LPS-stimulated MMC with IL-10 and IL-4 but not IL-13 suppressed NO production by HT-29 cells. Interestingly, pretreatment of HT-29 cells with IL-1 receptor antagonist suppressed the IFN-γ/LPS-stimulated MMC-induced NO production. These results suggest that immunomodulatory cytokines might exert an inhibitory effect on NO up-regulation by colonic epithelium via the inhibition of MMC-derived soluble mediators, such as IL-1.     

益生菌在儿童炎症性肠病中的应用

炎症性肠病（inflammatory bowel disease,IBD）是一种原因不明的慢性非特异性肠道炎性疾病,主要包括溃疡性结肠炎（ulcerative colitis,UC）、克罗恩病（Crohn's disease,CD）和未定型的炎症性肠病（IBD-unclassified,IBDU）。随着对肠道微生物与IBD关系认识的不断加深,许多研究发现肠道菌群的生态失调在IBD的发病中起着重要作用。益生菌在儿童IBD治疗中具有良好前景,但仍缺乏有效的证据来确证益生菌疗效,并指导临床对益生菌的种类和剂量等进行选择。现有研究表明,益生菌对儿童IBD的治疗具有特异性,在诱导和维持UC缓解效果明显,但在诱导CD缓解、维持CD缓解和预防术后并发症及复发方面效果并不理想。     

益生菌在炎症性肠病中的治疗作用

炎症性肠病(inflammatory bowel disease,IBD)包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。随着对肠道微生物群在IBD发病机制中作用的认识不断深入,近年来益生菌广泛应用于IBD治疗。大量临床试验结果表明,益生菌治疗IBD的疗效主要体现在对UC和贮袋炎的治疗,对CD的疗效不明确。益生菌治疗IBD可能通过促进肠道微生物群平衡、改善肠道屏障功能、调节肠道黏膜免疫及营养物质代谢等途径。     

肠内营养支持治疗对炎症性肠病患者肠黏膜屏障功能及炎症反应的影响

目的 探讨早期肠内营养（EN）支持治疗对炎症性肠病（IBD）患者肠黏膜屏障功能及炎症反应的影响。方法 将80例IBD患者按营养支持治疗途径分为EN组（48例）和肠外营养（PN）组（32例）,在常规治疗的基础上分别给予早期EN、PN支持治疗。比较治疗前后2组患者营养学相关指标[白蛋白（ALB）、前白蛋白（PA）、转铁蛋白（TF）]、肠黏膜屏障功能指标（内毒素、D-乳酸）及炎症相关指标[C-反应蛋白（CRP）、降钙素原（PCT）、粪便钙卫蛋白（FCP）]水平。结果 治疗前,2组患者各观察指标水平差异无统计学意义（P>0.05）;治疗后,与治疗前相比,2组患者血清ALB、PA及TF水平均显著升高（P0.05）。结论 在常规治疗的基础上,早期EN支持治疗对IBD患者肠黏膜屏障功能的改善及炎症缓解作用优于PN支持治疗。     

粪菌移植在儿童炎症性肠病中的应用

炎症性肠病（IBD）是一种病因尚不明确的非特异性肠道炎症性疾病。越来越多的证据表明肠道菌群失调与IBD的发生发展密切相关。粪菌移植是通过各种方式将健康捐赠者的粪便菌群移植入患者消化道内,旨在重建患者肠道菌群从而达到对肠道内外疾病治疗的目的。肠道微生物稳态及失调在疾病发生发展中发挥作用,其中包括炎症性肠病（IBD）。越来越多的研究报道了FMT在IBD中的治疗作用,现主要阐述粪菌移植在儿童IBD中的应用。     

Increased disease activity in eNOS-deficient mice in experimental colitis

Oral dextran sodium sulfate (DSS, 3%) produces experimental colitis with many features of human inflammatory bowel disease (IBD), (leukocyte extravasation, cachexia, and histopathology). Previous studies suggest that the inducible nitric oxide synthase (iNOS) in blood cells or in the endothelium contribute to this injury. However, until now no study has been performed to directly evaluate the role of endothelial nitric oxide synthase (eNOS) in IBD. We compared disease activity in wild-type (eNOS^+/+) and eNOS-deficient (eNOS^−/−) mice in the DSS model of colitis. Administration of DSS induced weight loss, stool blood, and overt histopathology in both mouse strains. Disease activity was dramatically increased in eNOS^−/− mice compared to wild types. Histologically, eNOS-deficient mice had greater leukocyte infiltration, gut injury, and expressed higher levels of the mucosal addressin, MAdCAM-1. These results demonstrate that eNOS plays an important role in limiting injury to the intestine during experimental colitis and altered eNOS content and/or activity may contribute to human IBD.     

益生菌在炎症性肠病治疗中的研究进展

益生菌（Probiotics）是一类能够促进肠道微生物菌群平衡,对宿主健康或生理功能产生有益作用的活性微生物。目前广泛应用于生命健康领域、科学研究、生物工程、工农业以及食品安全。大量国内外研究表明益生菌在降血压、降血糖、降血脂、抗过敏、抗炎、调节免疫、维持肠道菌群平衡等方面具有积极作用。炎症性肠病的病因和发病机制尚未完全明确,现多认为与遗传、环境、感染、免疫以及肠道微生物多因素相互作用有关。益生菌通过多种机制介导,在临床治疗炎症性肠病中扮演着重要角色。     

肠道微生物群落与炎症性肠病关系研究进展

目的炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC）,以持续性肠道非特异性炎症为特征,通常反复发作、迁延不愈,临床上仍无特效性的治疗手段。IBD确切的发病机制尚不清楚,涉及免疫、环境及遗传等因素,这些因素共同诱导肠道炎症、黏膜损伤和修复。肠道微生物群落及其代谢产物、宿主基因易感性及肠道黏膜免疫三方面共同参与了IBD的发病机制。本文从消化道微生态角度出发,对目前IBD相关的肠道微生物群落研究现状、宿主-微生物间免疫应答及益生菌治疗等内容进行探讨。     

炎症性肠病与肠道微生态的研究进展

炎症性肠病(inflammatoryboweldisease,IBD)是一种肠道慢性炎症性疾病,其发病机制尚不清楚。然而,IBD的发病率不断上升给患者及其家属带来了巨大的经济负担,需要找到积极有效的治疗方法来帮助患者。最新的观点认为,宿主和肠道微生物之间的平衡被打破会触发遗传易感个体的免疫炎症反应。肠道菌群失调在炎症性肠病的发病及发展过程中起着重要的作用。临床研究发现,IBD患者肠道菌群失调程度不同,而联合应用益生菌可以改善这些患者的症状。越来越多的研究者密切关注肠道菌群与IBD的关系,并进行了深入的基础和临床研究。本文从肠道菌群对IBD的生理影响以及益生菌和粪便细菌移植等方面进行综述。     

Hypoxia and inflammatory bowel disease

Inflammatory bowel disease (IBD) is a general term to describe inflammatory diseases of the gastrointestinal tract such as Crohn's disease and ulcerative colitis. IBD affects approximately 1 in 200 individuals and exerts a significant health and quality of life burden on patients. Surgical intervention can be curative in ulcerative colitis but there is currently no cure for Crohn's disease. Since this is the case, and the fact that patients are often diagnosed at a young age, IBD exerts a significant financial burden on the health care system, and society as a whole.The underlying pathology of IBD is complex and involves a combination of genetic, environmental and microbial factors. Regardless of the underlying causes of the condition, this disease is universally characterized by disruption to the protective epithelial barrier separating the intestinal lumen above from the mucosal immune system below. Once this barrier becomes compromised a sequence of events ensues, that can occur in repetitive cycles to ensure long-term and serious damage to the gut.The role of hypoxia and hypoxia-dependent signalling pathways are increasingly appreciated to play a role in the physiology and pathophysiology of the intestine. The intestinal epithelium normally exists in a state of physiological hypoxia, with additional tissue hypoxia a feature of active inflammatory disease. Furthermore, recent pre-clinical animal studies have clearly supported the rationale for pharmacologically manipulating the oxygen-sensitive hypoxia-inducible factor (HIF) pathway in models of IBD. Thus, this review will discuss the contribution of hypoxia sensitive pathways in the pathology of IBD. Finally we will discuss the emerging evidence for manipulation of hypoxia-sensitive pathways in the treatment of IBD.