Th17与炎症性肠病

溃疡性结肠炎（ulcerative colitis,UC）和克罗恩病（Crohn＇s disease,CD）是炎症性肠病（inflammatory bowel disease,IBD）的主要表现形式,发病机制尚不清楚。以往研究认为与T辅助细胞Th1或Th2细胞反应的增强或减弱有关。然而最近研究发现一类新细胞亚群,称为Th17细胞。Th17细胞的相关细胞因子可导致多脏器病变,包括肠道。Th17细胞反应需要IL-23的参与,IL-23在炎症性肠病患者肠道内过度表达解释了肠组织损伤的新途径以及制定新的治疗策略。     

Th17细胞在炎症性肠病中的作用及其临床价值

辅助性T细胞传统上分为Thl型和Th2型,然而近年人们又发现了一种具有与Thl和Th2细胞亚群完全不同分化机制和功能特性的新的CD4^＋T细胞亚群,2005年将其正式命名为Thl7细胞（Thelper 17 cell）。研究显示,     

细胞凋亡失调与炎症性肠病

细胞凋亡失调可导致肿瘤、自身免疫性疾病的发生。炎症性肠病（IBD）包括溃疡性结肠炎（UC）和克罗恩病（CD）,其发病机制尚未十分明确,可能与自身免疫功能紊乱有关。目前认为肠黏膜细胞凋亡失调在IBD的发病中占有十分重要的地位,肠黏膜上皮细胞凋亡过度、肠黏膜固有层T淋巴细胞和中性粒细胞凋亡迟滞可能是IBD发生及发展的原因之一,本文就细胞凋亡失调在IBD发病机制中作用的研究进展作一综述。     

炎症性肠病

炎症性肠病（inflammatory bowel disease,IBD）包括溃疡性结肠炎（uicerative colitis,UD）和克罗恩病（Crohn disease,CD）。CD又称局限性肠炎（regional enterites）、节段性肠炎,也有称为肉芽肿性结肠炎。19世纪30年代Crohn等人在美国医学会杂志上发表文章首次描述了该病的一些临床特征,到60年代中期Lockhaa-Mummery等人详细观察了本病的肠道病特征,并率先提出与其他疾病肠道病变的鉴别要点,至1973年WHO专门委员会定名为Crohn病。     

炎症性肠病

概念炎症性肠病有“广义”与“狭义”两种概念。“广义”统指病因明确与尚不明确的各种肠道炎症。“狭义”仅指病因不明的一些特殊类型的慢性肠道炎症,即所谓非特异性炎症性肠病。通常说到“炎症性肠病”(inflammatory bowel disease,简称IBD)均指这一类而言,包括克隆病,溃疡性结肠炎     

炎症性肠病与血栓症

炎症性肠病与血栓症胡坚方（江西省人民医院，南昌３３０００６）ＩｎｆｌａｍｍａｔｏｒｙＢｏｗｅｌＤｉｓｅａｓｅａｎｄＴｈｒｏｍｂｏｓｉｓＨｕＪｉａｎｆａｎｇ（ＪｉａｎｇｘｉＰｅｏｐｌｅ＇ｓＨｏｓｐｉｔａｌ，Ｎａｎｃｈａｎｇ３３０００６）炎症性肠病（Ｉｎ...     

益生菌与炎症性肠病

炎症性肠病(IBD)包括克罗恩氏病(CD)和溃疡性结肠炎(UC)，其病因和发病机制目前尚不清楚。临床研究发现，炎症性肠病患者肠道内存在菌群失调，正常细菌的数鼍减少，若给患者补充正常细菌即益生菌，使肠道内菌群失调得到纠正，可使病情缓解。1992年Fuller将益生菌定义为：经饮食摄取的能促进宿主机体微生态平衡的活微生物。本文就肠道菌群在炎症性肠病发病中的作用、益生菌对炎症性肠病的治疗作用作一简要综述。     

炎症性肠病与骨质疏松

<正>炎症性肠病(inflammatory bowel disease,IBD)是以反复发作的慢性肠道炎症为特点的一组疾病,主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn disease,CD),同时伴有多种肠道外表现。骨质疏松症是一种以骨量低下、骨微结构破坏、骨脆性增加、易发生骨折为特征的全身性骨病,同时也是IBD严重却     

炎症性肠病－－炎症性肠病的中医治疗

1　何谓“炎症性肠病”　　广义的“炎症性肠病”是指以肠道炎症为主要表现的不同疾病的总和 ;狭义的“炎症性肠病”(inflammatoryboweldisease ,IBD)包含了两个独立的疾病 :溃疡性结肠炎 (ulcerativecolitis ,UC)和克罗恩病 (Crohn’sdisease ,CD ) [1] 。IBD在西方国家相当常见 ,患病率达 40 /10万～ 10 0 /10万 ,在中国发病率比欧美低 ,但近年来该病的发病率有增加的趋势。近 2 0年来CD的增加更为明显 ,与UC的发病率、患病率几乎相当。国内由于过去一直认为本病少见而重视不够 ,但仅近 10年来医学文献报道即己逾千篇 ,累计病例超过…     

Th17-cytokine blockers as a new approach for treating inflammatory bowel disease

Anti-cytokine therapies, including the anti-TNF-α antibody-based therapies, have largely transformed the management of patients with inflammatory bowel diseases (IBD). However, benefit is seen in nearly 50% of patients, and response can wane with time. Moreover, patients treated with anti-TNF-α antibodies can develop severe side-effects and new immune-mediated diseases. Therefore enormous effort has been made by the research community to elucidate new inflammatory networks in the IBD tissue and to develop novel anti-cytokine compounds, which may act in patients who do not respond to or cannot receive anti-TNF-α therapies. In this article we review the available data supporting the pathogenic role of Th17 cytokines in IBD, and discuss whether and how inhibitors of these inflammatory mediators may enter into the therapeutic armamentarium of IBD.     

Nitric oxide and inflammatory bowel diseases

Nitric oxide (NO) production, as detectable by indirect and direct methods, as well as the expression of inducible nitric oxide synthase (iNOS) in the intestinal mucosa appear to be enhanced in active ulcerative colitis and, when in excess, to play a proinflammatory role in the disease. Despite some conflicting data, there is evidence that NO production is also increased in Crohn's disease. Many inflammatory features of inflammatory bowel disease are in keeping with the physiological properties of NO, and toxic megacolon, a complication of chronic colitis characterized by acute colonic dilatation, is associated with an enhanced intestinal synthesis of NO.   The drugs currently used in the treatment of inflammatory bowel disease (steroids, salicylates) do not seem to exert substantial effects on intestinal NO synthesis. The possible therapeutic role of selective iNOS inhibitors is still under investigation     

Th17细胞在肝脏疾病中的作用机制

T辅助17(Th17)细胞是新发现的T辅助细胞亚群,以分泌白细胞介素(IL)~(-1)7为特征,功能和发育上不同于Th1细胞和Th2细胞。肝脏是转化生长因子和IL-6的重要来源,而IL-6是对于Th17分化至关重要的细胞因子,另外,IL-17+细胞的频率自身免疫性肝病、病毒性肝炎和肝细胞癌等各种肝病中显著升高。推测Th17细胞参与各种肝病的发生发展。     

Bone alterations in inflammatory bowel diseases

Inflammatory bowel diseases (IBDs) are characterized by a multifactorial partially unknown etiology that involves genetic, immunological and environmental factors. Up to 50% of IBD patients experience at least one extraintestinal manifestation; among them is the involvement of bone density which is referred to as metabolic bone disease (MBD), including osteopenia and osteoporosis. Bone alterations in IBDs population appear to have a multifactorial etiology: Decreased physical activity, inflammation-related bone resorption, multiple intestinal resections, dietary malabsorption of minerals and vitamin D deficiency, genetic factors, gut-bone immune signaling interaction, steroid treatment, microbiota and pathogenic micro-organisms interaction, and dietary malabsorption of minerals, that, all together or individually, may contribute to the alteration of bone mineral density. This review aims to summarize the prevalence and pathophysiology of metabolic bone alterations in IBD subjects outlining the main risk factors of bone fragility. We also want to underline the role of the screening and prophylaxis of bone alterations in Crohn’s disease and ulcerative colitis patients and the importance of treating appropriately MBD.     

Post-genome challenges against inflammatory bowel diseases

Advancement of genome analysis might give great impact to the treatment of inflammatory bowel diseases(IBD). IBD patients are treated by sulfadrugs, steroids and anti-immune drugs. For difficult cases, leukocytapheresis, beclomethasone dipropionate, anti-TNF therapy, anti-LTB4 therapy and other new methods are applied. Developing epoch-making drugs will be achieved by finding new molecular targets. Histologic identification of dysplasia is important in the surveillance of long-standing ulcerative colitis. The molecular diagnosis is required for the distinction of dysplasia from the regenerative inflammatory changes. P53 immunostaining have been proved useful. Various molecular targets will be taken into discussion as additional procedures. Recent genome analysis have revealed some genetic factors contribute to pathogenesis of IBD, which are HLA, IL4, MUC3, IBD1 locus, IBD2 locus and so on. More information about genes concerning IBD will be provided by analyzing dense SNP map using DNA tip. They will open the way to the tailored therapy.     

Immunotherapeutic approaches to inflammatory bowel diseases

For a long time corticosteroids, aminosalicylic acid preparations and antibiotics have represented the principal approaches in evidence-based drug therapy for chronic inflammatory bowel diseases (IBD), e.g., Crohn’s disease (CD) and ulcerative colitis (UC), and are able to suppress disease activity in most cases. However, there are cases that do not respond to conventional drug therapy or remain dependent on high doses of steroids associated with severe side effects in the long run. It is generally accepted now that IBD has an immunological basis and results from a hyper-responsive state of the intestinal immune system. Although the primary etiological defect respectively immunogenic agent still remains to be identified, substantial progress has been made in our understanding of regulatory mechanisms of the intestinal immune system and their alterations in IBD at the molecular level. Due to the concurrent advent of biotechnological processes it has been possible to utilise these insights for the development of novel immunomodulatory therapeutic strategies ranging from recombinant cytokines and blocking antibodies to oligonucleotide antisense strategies and gene therapeutic approaches. This review will present the current status of the development of these novel immunomodulatory therapeutic strategies in IBD and the status of their use in clinical practice. For a better understanding, it will be necessary to address the recent advances in the elucidation of pathogenetic mechanisms of IBD from studies in human specimen and experimental colitis models that have provided the basis for these novel therapeutic approaches.     

Alpha1-antitrypsin deficiency and inflammatory bowel diseases

OBJECTIVE: To evaluate a possible etiologic role of alpha1-antitrypsin deficiency (alpha1AD), most frequently caused by a Z allele mutation, in ulcerative colitis (UC) and Crohn disease (CD). PATIENTS AND METHODS: This retrospective study included 10 patients diagnosed with and/or treated for inflammatory bowel disease (IBD) between 1976 and 1997 and identified from the Mayo Clinic Medical Index System. All 10 patients had either alpha1AD and CD or alpha1AD and UC. The alpha1-antitrypsin (alpha1AT) types and levels were determined with isoelectric focusing testing. The allele types, representing genotypes, were designated PiZZ (or ZZ) for homozygotes and PiMZ (or MZ) for heterozygotes. RESULTS: Seven patients had UC: 4 were genotype ZZ and 3 MZ. Four of these 7 patients had emphysema, 2 had asthma, and 1 had chronic bronchitis. Five were cigarette smokers, but only 1 had smoked coincident with activity of her UC. Two of the UC patients never smoked, and 1 of these 2 had asthma. Three of the 10 patients had CD, 2 genotype ZZ and 1 MZ. Two of the 3 patients were long-term cigarette smokers, and both had emphysema. Nine of the 10 patients with UC and alpha1AD required surgery. CONCLUSIONS: The need for surgery in patients with UC and alpha1-AD may point to a unique phenotypic subgroup of patients with alpha1AD and severe UC. Further studies are required to substantiate the etiologic role of alpha1AD in IBD. Our observations, if confirmed by future studies, suggest that in patients with both IBD and chronic obstructive pulmonary disease, alpha1AD testing should be considered.     

Rheumatologic and extraintestinal manifestations of inflammatory bowel diseases

Inflammatory bowel diseases (IBDs) often present as a complex inflammatory process wherein colon lesions (ulcerative colitis, UC) or widespread ulceration and fissure (Crohn’s disease, CD) might be accompanied by ancillary extraintestinal manifestations (EIMs) that could involve almost every organ system, but also by autoimmune disorders ranging from psoriasis and rheumatoid arthritis to connective tissue diseases. Certain EIMs are more common related to the activity of the IBD (joint, skin, ocular and oral manifestations), other EIMs typically run a course independent of the IBD activity (hepatobiliary disorders) and some are non-specific disorders (osteoporosis and amyloidosis). This paper reviews the most common extraintestinal and rheumatologic manifestations of UC and CD. They may produce greater morbidity than the underlying intestinal disease and may even be the initial presenting symptoms of the IBD. Thus, early recognition of these manifestations should help guide therapy that will reduce overall morbidity in affected patients.

• Key Message

• A complete review on the most common extraintestinal and rheumatologic manifestations of ulcerative colitis and Crohn’s disease.