Inflammatory Bowel Disease and Cytokine

Eun Young Choi(최은영),Kwang Keun Cho(조광근),In Soon Choi(최인순) 한국생명과학회 2013 생명과학회지 Vol.23 No.3

크론병과 궤양성 대장염으로 잘 알려져 있는 염증성 장질환은 재발과 호전을 반복하는 만성적인 염증 및 이에따른 합병증을 특징으로 하는 원인 불명의 질환이다. 염증성 장질환의 발생 원인은 아직 명확히 알려져 있지 않지만 흡연이나 식이와 같은 환경적 요인, 장내 세균총과 같은 미생물학적 요인, 면역 매개에 의한 조직 손상과 같은 면역학적 요인 그리고 유전학적 요인 등이 복합적으로 발생기전에 관여 할 것이라고 추정한다. 특히 사이토카인과 같은 염증매개물질에 의해 세포매개염증반응의 일련의 과정이 유발 혹은 증폭되거나, 면역 조절 기능의 면화로 장 점막의 국소적 조직 손상을 유발하게 되며 면역 및 염증 반응이 적절하게 감소되지 않고 지속되어 만성 염증에 이르게 된다. 최근 이러한 염증반응에 중요한 역할을 담당하는 사이토카인 유전자에 관심이 몰리고 있다. 사이토카인은 활성화된 면역세포에서 주로 생성되는 당단백으로서 분자량이 8~10 kD 정도이며, 면역 반응시 T세포, B세포, 대식세포 등의 면역세포 상호간에 활성화, 증식 및 분화 등에 관계하여 국소적 조직 손상 및 염증반응을 일으킨다. 반면에 장의 구조와 기능에 있어 중요한 기질인 식이 섬유소에서 유래되는 Butyrate는 친염증성 사이토카인을 감소시키고 항염증성 사이토카인을 증가시킴으로써 장관 면역계에 대한 조절기능을 보이고 있다. 따라서 본 총설에서는 Butyrate의 항염증 효과에 대한 분자적 기작을 면역세포에서 Butyrate가 가지는 사이토카인 조절 능력을 통해 이해하고 Butyrate가 염증성 장질환에 대해 새로운 치료 전략을 제시 해 줄 것으로 기대한다. Inflammatory bowel disease, known as Crohn’s disease and ulcerative colitis, is an unexplained disease characterized by chronic inflammation that repeats a cycle of relapse, improvement, and complications. The cause of inflammatory bowel disease is not clearly known, but it is predicted that a complex of various factors precipitate its occurrence. In particular, inflammatory mediators, such as cytokine, induce an increase in cell-mediated inflammatory responses. Focal tissue damage then occurs in the intestinal mucosa because of the weakening of the immune-modulating functions of cotton. Immune and inflammatory responses do not decrease appropriately but continue until they lead to chronic inflammation. Current research has focused on the cytokine genes, which have important roles in these inflammatory responses. Cytokine is a glycoprotein that is produced mostly in activated immune cells. It connects the activation, multiplication, and differentiation between immune cells, which causes focal tissue damage and inflammatory response. Moreover, butyrate, which originates in dietary fiber and plays an important role in the structure and function of the intestinal area, shows control functions in the intestinal immune system by decreasing the proinflammatory cytokine and increasing the anti-inflammatory cytokine. Therefore, this research investigated the molecular mechanism of the anti-inflammatory effects of butyrate to comprehend the cytokine controlling abilities of butyrate in the immune cells. Butyrate is expected to have potential in new treatment strategies for inflammatory bowel disease.

만성 염증성 장질환 및 감염성 대장염 환자의 대장상피 세포에서의 HLA - DR 항원 발현 양상

정현채(Hyun Chae Jung),이준혁(Joon Hyeok Lee),김우호(Woo Ho Kim),송인성(In Sung Song),최규완(Kyoo Wan Choi),김정룡(Chung Yong Kim),김정목(Jung Mogg Kim) 대한내과학회 1995 대한내과학회지 Vol.48 No.5

Objective: Since it was reported that expression of HLA-DR antigen by colonic epithelial cells was observed in inflammatory bowel disease, whether this phenomenon is specific for idiopathic inflammatory bowel disease has been controversial. Furthermore, studies concerning the expression of HLA-DR antigen in tuberculous colitis, one of the most common diseases which need differential diagnosis with idioapthic inflammatory bowel diseases in Korea, and Behcet's colitis, rare in Western countries, have not been reported as yet. The purposes of this study are to test the hypothesis that the expression of HLA-DR antigen by colonic epithelium is specific for idiopathic inflammatory bowel disease, and to observe the pattern of the colonic expression of HLA-DR antigen in Behcet's colitis and to compare with ulcerative colitis and Crohn's disease. Methods: Multiple colonoscopic biopsies were performed on fifty eight patients(twenty seven ulcerative colitis, four Crohn's disease, nine Behcet's colitis, nine infectious colitis, and nine normal control). Immunohistochemical staining using mouse monoclonal anti-HLA-DR antibody was performed on each biopsy specimens, and was compared according to its histologic activity. Results: 1) In the ulcerative colitis group, 77.2% of specimens with histologically active inflammation expressed HLA-DR antigen, whereas only 15.6% of specimens without active inflammation did, showing significant difference(p<0.005). 2) In the Crohn's disease group and the infectious colitis group, specimens with histologically active inflammation(58.3% and 60.0%) showed higher positive rate than specimens without histologically active inflammation(12.5% and 40.0%), but statistical significance was not observed(p>0.05). 3) Colonic epithelial cells of the Behcet's disease group expressed HLA-DR antigen only in 18.8% of specimens with histologically active inflammation, showing significantly lower rate of positive expression than other inflammatory bowel diseases with active inflammation(67.3%, p<0.005). 4) Overall, 52.2% of specimens with active inflammation expressed epithelial HLA-DR antigen, showing significantly higher rate of positive expression than specimens without active inflammation(19.8%, p<0.005). Conclusion: The epithelial expression of HLA-DR antigen in inflammatory bowel disease seems to be a nonspecific parameter indicating active histologic inflammation, especially in ulcerative colitis, and cannot be used in differential diagnosis of tuberculous colitis and Crohn's disease. However, in Behcet's colitis, the frequency of HLA-DR antigen expression by colonic epithelium is significantly lower than other inflammatory bowel disease, therefore a different immunopathophysiologic mechanism is suggested, which needs further investigation.

Predictors of Small Bowel Transit Time for Capsule Endoscopy in Children with Inflammatory Bowel Disease

Itsuhiro Oka,Rie Funayama,Hirotaka Shimizu,Ichiro Takeuchi,Shuko Nojiri,Toshiaki Shimizu,Katsuhiro Arai 대한소아소화기영양학회 2023 Pediatric gastroenterology, hepatology & nutrition Vol.26 No.4

Purpose: The development of assistive devices has allowed for the performance of capsule endoscopy in children. Anticipating the capsule’s transit time could affect the efficacy of the investigation and potentially minimize the fasting period. This study determined the predictors of small bowel transit time for small-bowel capsule endoscopy in children and adolescents with inflammatory bowel disease. Methods: We retrospectively examined children and adolescents with inflammatory bowel disease who underwent capsule endoscopy by the age 18 at a Japanese tertiary care children’s hospital. Small bowel transit time predictors were analyzed using multiple regression with explanatory variables. Results: Overall, 92 patients, aged 1–17 years, with inflammatory bowel disease (63 Crohn’s disease and 29 ulcerative colitis cases) were examined for factors affecting small bowel transit time. In the simple regression analysis, diagnosis, age, height, weight, serum albumin, general anesthesia, and small intestine lesions were significantly associated with small bowel transit time. In the multiple regression analyses, serum albumin (partial regression coefficient: −58.9, p=0.008), general anesthesia (partial regression coefficient: 127, p<0.001), and small intestine lesions (partial regression coefficient: 30.1, p=0.037) showed significant associations with small bowel transit time. Conclusion: Hypoalbuminemia, the use of general anesthesia for endoscopic delivery of the capsule, and small intestine lesions appeared to be predictors of prolonged small bowel transit time in children and adolescents with inflammatory bowel disease. Expecting the finishing time may improve examination with a fasting period reduction, which benefits both patients and caregivers.

Artificial intelligence in inflammatory bowel disease: implications for clinical practice and future directions

( Harris A. Ahmad ),( James E. East ),( Remo Panaccione ),( Simon Travis ),( James B. Canavan ),( Keith Usiskin ),( Michael F. Byrne ) 대한장연구학회 2023 Intestinal Research Vol.21 No.3

Inflammatory bowel disease encompasses Crohn’s disease and ulcerative colitis and is characterized by uncontrolled, relapsing, and remitting course of inflammation in the gastrointestinal tract. Artificial intelligence represents a new era within the field of gastroenterology, and the amount of research surrounding artificial intelligence in patients with inflammatory bowel disease is on the rise. As clinical trial outcomes and treatment targets evolve in inflammatory bowel disease, artificial intelligence may prove as a valuable tool for providing accurate, consistent, and reproducible evaluations of endoscopic appearance and histologic activity, thereby optimizing the diagnosis process and identifying disease severity. Furthermore, as the applications of artificial intelligence for inflammatory bowel disease continue to expand, they may present an ideal opportunity for improving disease management by predicting treatment response to biologic therapies and for refining the standard of care by setting the basis for future treatment personalization and cost reduction. The purpose of this review is to provide an overview of the unmet needs in the management of inflammatory bowel disease in clinical practice and how artificial intelligence tools can address these gaps to transform patient care. (Intest Res 2023;21:283-294)

염증장질환의 치료: 생물학적제제 및 새로운 치료법을 중심으로

송효엽,서검석 대한의사협회 2021 대한의사협회지 Vol.64 No.9

Background: The treatment of inflammatory bowel diseases has evolved with the development of anti-tumor necrosis factor agents. Despite the long-term effectiveness, many patients experience primary non-response, secondary loss of response, or intolerance. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. This review focuses on biologic agents and new therapies for the treatment of inflammatory bowel diseases. Current Concepts: Vedolizumab, a gut-selective agent that targets α4β7 integrin is effective in both ulcerative colitis and Crohn’s disease. Ustekinumab is a monoclonal antibody that binds to p40 subunit of interleukin-12/ interleukin-23. Ustekinumab is available for the treatment of Crohn’s disease and ulcerative colitis. Tofacitinib is the first Janus kinase inhibitor approved for the treatment of ulcerative colitis. The advantage of tofacitinib is an oral prescription medicine and has rapid action. Discussion and Conclusion: Since vedolizumab, ustekinumab and tofacitinib are effective agents for the treatment of inflammatory bowel diseases, positioning of old and new biologic agents and small molecules should be determined. The safety and efficacy of novel and emerging drugs needs to be evaluated in patients with inflammatory bowel disease.

Various skin manifestations related to inflammatory bowel disease: A nationwide cross-sectional study on the Korean population

( Ui Hyeon Jo ),( Jin Yong Lee ),( Hanjae Lee ),( Do-yeop Kim ),( Sungchan Kang ),( Seong-joon Koh ),( Hyunsun Park ) 대한피부과학회 2020 대한피부과학회 학술발표대회집 Vol.72 No.1

Background: Inflammatory bowel disease (IBD) presents with various extraintestinal manifestations, especially skin diseases. Objectives: We aimed to identify the epidemiology and risk of developing skin manifestations in patients with IBD. Methods: We used Korean National Health Insurance Claims database and selected patients with IBD and age/sex-matched non-IBD subjects using the diagnosis code and prescription records of IBD-specific medications from 2013 to 2017. The prevalence and risk of concurrent skin diseases were estimated. Results: A total of 64,837 patients with IBD was identified. Among 3 categories of reactive, inflammatory, and autoimmune skin diseases, reactive skin eruptions including pyoderma gangrenosum and erythema nodosum were associated with IBD with highest odds ratios. Inflammatory skin diseases including rosacea, psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne conglobata were significantly associated with IBD. The patients with IBD also had a higher risk of autoimmune skin diseases including vitiligo and alopecia areata than non-IBD subjects. Conclusion: This population-based study suggests that IBD was related to various skin diseases including reactive, inflammatory, and autoimmune skin diseases. Considering these relationships can allow better management of patients with IBD and comorbid skin diseases.

A Comprehensive Review of Inflammatory Bowel Disease Focusing on Surgical Management

백승혁,김원호 대한대장항문학회 2012 Annals of Coloproctolgy Vol.28 No.3

The two main diseases of inflammatory bowel disease are Crohn’s disease and ulcerative colitis. The pathogenesis of inflammatory disease is that abnormal intestinal inflammations occur in genetically susceptible individuals according to various environmental factors. The consequent process results in inflammatory bowel disease. Medical treatment consists of the induction of remission in the acute phase of the disease and the maintenance of remission. Patients with Crohn’s disease finally need surgical treatment in 70% of the cases. The main surgical options for Crohn’s disease are divided into two surgical procedures. The first is strictureplasty, which can prevent short bowel syndrome. The second is resection of the involved intestinal segment. Simultaneous medico-surgical treatment can be a good treatment strategy. Ulcerative colitis is a diffuse nonspecific inflammatory disease that involves the colon and the rectum. Patients with ulcerative colitis need surgical treatment in 30% of the cases despite proper medical treatment. The reasons for surgical treatment are various,from life-threatening complications to growth retardation. The total proctocolectomy (TPC) with an ileal pouch anal anastomosis (IPAA) is the most common procedure for the surgical treatment of ulcerative colitis. Medical treatment for ulcerative colitis after a TPC with an IPAA is usually not necessary.

Is Curcumin a Possibility to Treat Inflammatory Bowel Diseases?

Rafaela Mazieiro,Renata Reis Frizon,Sandra Maria Barbalho,Ricardo de Alvares Goulart 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.11

The inflammatory bowel diseases (IBDs) are mainly represented by Crohn's disease and Ulcerative colitis that are characterized by chronic and relapsing inflammatory processes of the gastrointestinal system. Curcuma longa L. is a plant with several medicinal properties, including anti-inflammatory effects, and curcumin is the most important compound derived from its rhizomes. As curcumin has remarkable anti-inflammatory actions, the aim of this work is to review the potential use of this compound in IBD patients. We consulted MEDLINE (PubMed/PMC), and the literature search was performed with the following combinations of terms “Inflammatory Bowel Diseases” and “Curcumin,” “Crohn's Disease” and “Curcumin,” “Ulcerative colitis” and “Curcumin.” The inclusion criteria were articles that showed original studies with human models and the exclusion criteria were not full-text articles, articles not in English, poster presentations, letters, editorials, and articles not available. Curcumin interacts with receptors, growth and transcription factors, cytokines, enzymes, and genes leading to inhibitory effects on cyclooxygenase-1, tumor necrosis factor-α, interferon-γ, inducible nitric oxide synthase, transcriptional nuclear factor kappa B, and many other molecules associated with inflammatory processes. These molecules are critical factors in the positive regulation of inflammatory cytokines in inflammatory diseases, suggesting that curcumin may be considered as a new therapeutic agent for patients with IBD. Curcumin is a natural anti-inflammatory agent that represents an attractive, safe and inexpensive alternative for the treatment of IBD. Nevertheless, it is necessary to know the efficient and safe dose and consider its poor absorption.

REVIEW : Role of Intestinal Microbiota in Inflammatory Bowel Diseases

( Chang Soo Eun ) 대한장연구학회 2013 Intestinal Research Vol.11 No.3

A vast number of micro-organisms within the human gut play a crucial role in maintaining human health. Intestinal microbiota maintains the intestinal homeostasis and function by mutually interacting with the host`s epithelial cells and mucosal immune system; and the immune tolerance towards intestinal commensals should be permitted for such interactions to occur. In recent years, the prevalence of inflammatory bowel diseases has greatly increased, and the pathogenic pathway behind is considered to be related to an aggressive immune response which is a subset of commensal enteric bacteria in a genetically susceptible host. The abnormal host-microbial interactions play an important role in the pathophysiology of inflammatory bowel diseases, which have been proved through numerous studies in the field of genetics, molecular microbiology, immunology, and experimental rodent models, as well as various translational researches and clinical trials. This review briefly summarizes the composition and function of intestinal microbiota, interactions between the microbiota and the immune system, and the possible roles of the intestinal microbiota in the pathogenesis of inflammatory bowel diseases. (Intest Res 2013;11:161-168)

Systematic Review of Recent Lipidomics Approaches Toward Inflammatory Bowel Disease

( Eun Goo Lee ),( Young Cheol Yoon ),( Jihyun Yoon ),( Seul Ji Lee ),( Yu-kyoung Oh ),( Sung Won Kwon ) 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.6

Researchers have endeavored to identify the etiology of inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis. Though the pathogenesis of inflammatory bowel diseases remains unknown, dysregulation of the immune system in the host gastrointestinal tract is believed to be the major causative factor. Omics is a powerful methodological tool that can reveal biochemical information stored in clinical samples. Lipidomics is a subset of omics that explores the lipid classes associated with inflammation. One objective of the present systematic review was to facilitate the identification of biochemical targets for use in future lipidomic studies on inflammatory bowel diseases. The use of high-resolution mass spectrometry to observe alterations in global lipidomics might help elucidate the immunoregulatory mechanisms involved in inflammatory bowel diseases and discover novel biomarkers for them. Assessment of the characteristics of previous clinical trials on inflammatory bowel diseases could help researchers design and establish patient selection and analytical method criteria for future studies on these conditions. In this study, we curated literature exclusively from four databases and extracted lipidomics-related data from literature, considering criteria. This paper suggests that the lipidomics approach toward research in inflammatory bowel diseases can clarify their pathogenesis and identify clinically valuable biomarkers to predict and monitor their progression.