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

N/A 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.

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.

탈진적 운동부하가 염증성 장 질환 모델 흰쥐의 염증성 사이토카인 및 대장운동성에 미치는 영향

조민호(Cho, Min-Ho),전윤수(Jeon, Yun-Su) 한국체육과학회 2015 한국체육과학회지 Vol.24 No.5

This experiment was conducted to define the exercise effect of inflammatory bowel disease(IBD). For this purpose we used the IL10 knock out mouse which is an experimental animal for IL10 Gene conversion trait, and categorized each control group(CON, n=7), control and exercise(CONEX, n=7), IL10 knock out (IL10KO, N=7), IL10 knock out and exercise(IL10KOEX, n=7) to excess the alteration of concentrations of inflammatory cytokine in the blood due to the exhaustible exercise. As a result, in case of the alteration of the inflammatory cytokine, IL-6, TNFα and MMP-2 showed a noticeable increase due to the exhaustible exercise compared to the CON in the gene conversion trait. This may be because the inflammatory cytokines are more reliant to the conversion of traits than the motion load. Only in case of the MMP-2"s the increase in blood concentration was shown not only in the experimental animal group but also in the exhausted exercise caused by CONEX. Meanwhile, changes of contractions of bowel segment cause by chemical reaction was shown decrease in IL10KOEX regardless to the cholinergic response and nitric acid auxiliary, which is meaningless to statistics. In conclusion, according to the result of the one-time experiment, which is the exhausted exercise conducted towards experimental animal, showed damages in intestinal mucosa"s tissue and decreased the contraction of the bowel due to the increase in inflammatory cytokine. In other words, the one-time exhausted exercise have caused the escalation of the inflammatory response regarding the inflammatory bowel disease. However, it is conceivable that later it will be imperative to have an experiment that compares the high intensity exercise and the low intensity exercise. This is an experiment that is crucial for defining the effect of exercising towards inflammatory bowel disease. There are limits to this; clinical demonstration is hard due to the characteristics of the disease; it is hard to obtain experimental animal as a model. However, even though, this is a short trial regarding inflammatory bowel disease I believe it will be a rudimentary data for experiments that deals with experimental animals.

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.

Immunomodulatory and Anti-Inflammatory Phytochemicals for the Treatment of Inflammatory Bowel Disease (IBD): Turning Strong Rationale into Strong Evidence?

Hamid Reza Sodagari,Zahra Aryan,Amir Hossein Abdolghaffari, Nima Rezaei,Nima Rezaei,Amirhossein Sahebkar 대한약침학회 2018 Journal of pharmacopuncture Vol.21 No.4

Inflammatory bowel disease (IBD) comprises two types of chronic and relapsing intestinal inflammation conditions including Crohn’s disease and ulcerative colitis [1]. Although the exact etiology of IBD remains elusive, the interaction of host’s immune system with diet and microbiome of intestinal tract in genetically susceptible individuals seems to play a pivotal role in the pathogenesis of IBD [2]. Encoding regions for nucleotide oligomerization domain 2 (NOD2) and interleukin 23 T helper 17 (Th17) pathway are the most prominent genetic components of IBD pathogenesis [3,4]. NOD2 recognizes bacterial peptidoglycan and triggers the inflammatory cascade [5], and interleukin 23 is integral to immune defense against non-self-antigens and chronic intestinal inflammation [6]. On the other hand, breakdown and alteration of normal microbiome increases the risk of intestinal colonization with pathogenic organisms and inflammatory diseases [7]. Dietary factors are known to influence gut microbiome and have the potential to shape the interplay between gut microbiome and immune responses involved in the pathogenesis of IBD [2]. Dietary factors can affect gut colonization of microorganisms in long term; they can mimic pathogenic antigens and trigger intracellular transduction and transcription pathways leading to modulation of inflammatory responses [8,9]. Exposure to stimuli such as reactive oxygen species, bacterial antigens and even innocent antigens activate nuclear factor (NF)-κB. This cascade results in the production of chemokines, pro-inflammatory cytokines, and infiltration of lymphocytes to the intestinal mucosa and disturbance of epithelial barrier leading to chronic intestinal inflammation. Phytochemicals including ellagic acid, curcumin, flavonoids, quercetin and green tea polyphenols can modulate NF-κB pathway [10-14]. Besides cytokine overproduction, overexpression of COX-2, the rate-limiting enzyme of prostaglandin production, is also involved in either acute or chronic intestinal inflammation. Phytochemicals such as grape juice and black raspberry powder have the ability to inhibit COX-2 and prostaglandin production [15,16]. Research on immunomodulatory and anti-inflammatory activities of phytochemicals in preventing and treating intestinal inflammation, and in modulating the gut microbiome and colitis symptoms is still at its infancy. Most of the evidence have come from animal studies [10-16], thus evidence from well-designed randomized controlled trials in this area are lacking. The shortcomings of available drugs to treat IBD and their side effects highlight a real need to additional therapies that could confer, either as alternative or adjunct, a better control of disease. In this context, phytochemicals are interesting candidates owing to their multimechanistic mode of action, potential safety, and wide availability [1,2]. Moreover, limited bioavailability of phytochemicals which is generally considered as an obstacle against their maximal systemic effects is less of a problem in IBD, as the site of action is intestine where the phytochemical is almost completely bioavailable upon oral use. While all these points emphasize the great therapeutic potential of phytochemicals for the treatment of IBD, important questions as to the dose-response association, clinical efficacy, precise mechanism(s) of action, and long-term tolerability still remain to be answered.

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)

Inflammatory bowel disease (IBD)-disk accurately predicts the daily life burden and parallels disease activity in patients with IBD

( Arshdeep Singh ),( Yogesh Kumar Gupta ),( Ashvin Singh Dhaliwal ),( Bhavjeet Kaur Kahlon ),( Vasu Bansal ),( Ramit Mahajan ),( Varun Mehta ),( Dharmatma Singh ),( Ramandeep Kaur ),( Namita Bansal ) 대한장연구학회 2023 Intestinal Research Vol.21 No.3

Background/Aims: The inflammatory bowel disease (IBD)-disk is a validated, visual, 10-item, self-administered questionnaire used to evaluate IBD-related disability. The present study aimed to evaluate IBD-disk in assessment of IBD daily life burden and its relation with disease activity. Methods: A cross-sectional study was conducted between June 2021 and December 2021. Patients with IBD were asked to complete the IBD-disk and a visual analogue scale of IBD daily-life burden (scored from 0-10, score >5 indicative of high burden). The internal consistency of IBD-disk, correlation with IBD daily life burden and disease activity (assessed by partial Mayo score and Harvey Bradshaw Index in patients with ulcerative colitis [UC] and Crohn’s disease [CD], respectively) and diagnostic performance of IBD-disk to detect high burden were analyzed. Results: Out of the 546 patients (mean age 40.33±13.74 years, 282 [51.6%] males) who completed the IBD-disk, 464 (84.98%) had UC and the remaining (n=82, 15.02%) had CD. A total of 311 patients (291 UC and 20 CD; 56.95%) had active disease. The mean IBD-disk total score and IBD daily life burden were 18.39±15.23 and 2.45±2.02, respectively. The IBD-disk total score correlated strongly with the IBD daily life burden (ρ=0.94, P< 0.001), moderately with partial Mayo score (ρ=0.50) and weakly with Harvey Bradshaw Index (ρ=0.34). The IBD-disk total score >30 predicted high IBD daily-life burden. Conclusions: The IBD-disk accurately predicts the daily life burden and parallels disease activity in patients with IBD and can be applied in clinical practice. (Intest Res 2023;21:375-384)

Adverse Events Associated with Azathioprine Treatment in Korean Pediatric Inflammatory Bowel Disease Patients

천지영,강빈,이유민,이수연,김미진,최연호 대한소아소화기영양학회 2013 Pediatric gastroenterology, hepatology & nutrition Vol.16 No.3

Purpose: This study was aimed to evaluate the frequency and course of adverse events associated with azathioprine treatment in Korean pediatric patients with inflammatory bowel disease. Methods: Total of 174 pediatric patients (age range, 1 to 19 years) with inflammatory bowel disease who received azathioprine in order to maintain remission at Samsung Medical Center (Seoul, Korea) from January 2002 through December 2012 were included in this study. Medical records of these subjects were retrospectively reviewed regard-ing the development of adverse events associated with azathioprine treatment.Results: Ninety-eight patients (56.3%) of 174 patients experienced 136 episodes of adverse events, requiring dose reduction in 31 patients (17.8%), and discontinuation in 18 patients (10.3%). The mean dose of azathioprine that had been initially administered was 1.32±0.42 mg/kg/day. Among the adverse reactions, bone marrow suppression developed in 47 patients (27.0%), requiring dose reduction in 22 patients (12.6%) and discontinuation in 8 patients (4.6%). Other adverse events that occurred were gastrointestinal disturbance (15.5%), hair loss (12.1%), pancreatitis (7.5%), arthralgia (6.9%), hepatotoxicity (2.9%), skin rash/allergic reactions (2.9%), headache/dizziness (2.3%), sepsis (0.6%), and oral mucositis (0.6%). Conclusion: Bone marrow suppression, especially leukopenia was most commonly associated with azathioprine treatment in Korean pediatric inflammatory bowel disease patients. Close observation for possible adverse events is required in this population with inflammatory bowel diseases who are under treatment with azathioprine. (Pediatr Gastroenterol Hepatol Nutr 2013; 16: 171∼177)

The Relationship between Quiescent Infl ammatory Bowel Disease and Peripheral Polyneuropathy

( Zuleyha Akkan Cetinkaya ),( Yılmaz Cetinkaya ),( Mehmet Gencer ),( Mesut Sezikli ),( Hulya Tireli ),( Oya Ovunc Kurdas ),( Kayıhan Uluc ),( Onder Us ),( Tulin Tanrıdag ) 대한소화기기능성질환·운동학회 2011 Gut and Liver Vol.5 No.1

Background/Aims: Infl ammatory bowel disease is a chronic, recurrent disorder that involves multiple organ systems. Polyneuropathy is the most common neurological manifestation. The aim of the present study was to investigate the relationship between polyneuropathy and infl ammatory bowel disease. Methods: The study included 40 patients with infl ammatory bowel disease (20 with ulcerative colitis and 20 with Crohn`s disease) and 24 healthy controls. The patients had no clinical signs or symptoms of polyneuropathy. Nerve conduction studies were performed using an electroneuromyography apparatus. Results: Mean distal motor latencies, conduction velocities, and F wave minimum latencies of the right median nerve were signifi cantly abnormal in the patient group, compared to the healthy controls (p<0.05). Conclusions: Some electrophysiological alterations were observed in chronic infl ammatory bowel disease patients who showed no clinical signs. While investigating extra-intestinal manifestations in inflammatory bowel disease patients, nerve conduction studies must be performed to identify electrophysiological changes and subclinical peripheral polyneuropathy, which can subsequently develop. (Gut Liver 2011;5:57-60)