Comparative analysis of the effects of anti-IL-6 receptor mAb and anti-TNF mAb treatment on CD4+ T-cell responses in murine colitis.

Abstract:

BACKGROUND:The efficacy of anti-tumor necrosis factor monoclonal antibody (anti-TNF mAb) for Crohn's disease (CD) is well established, and anti-interleukin-6 receptor (anti-IL-6R) mAb has also been reported to be effective in CD. It is, however, unclear if the efficacy and mechanisms of both agents are different in CD therapy. METHODS:Using an adoptive transfer colitis model, we compared the efficacy of anti-IL-6R mAb, anti-TNF mAb, and TNF receptor-Fc fusion protein (TNFR-Fc), and their modes of action on CD4+ T cells. We also investigated the role of Th1 and Th17 cells in colitis using the same model. RESULTS:The histological scores for the anti-IL-6R mAb and anti-TNF mAb groups but not for TNFR-Fc group were much lower than that for the control group, and the score was the lowest for the anti-IL-6R mAb group. The frequency of proliferating CD4+ T cells was reduced in anti-IL-6R mAb and anti-TNF mAb groups, but not in the TNFR-Fc group, whereas the frequency of apoptotic CD4+ T cells was similar in all groups. Anti-IL-6R mAb suppressed the induction of Th17 cells and increased the frequency of lamina propria regulatory T cells, whereas anti-TNF mAb exerted no influence on CD4+ T-cell differentiation. A deficiency in interferon-γ and/or IL-17 in CD4+ T cells reduced the severity of colitis. CONCLUSIONS:Our findings suggest that suppression of the proliferation of pathogenic CD4+ T cells is the major mode of action of biological agents for colitis therapy. Anti-IL-6R mAb might have benefits in CD patients with Th17 dominance and impaired Treg frequency.

journal_name

Inflamm Bowel Dis

authors

Terabe F,Fujimoto M,Serada S,Shinzaki S,Iijima H,Tsujii M,Hayashi N,Nomura S,Kawahata H,Jang MH,Miyasaka M,Mihara M,Ohsugi Y,Kishimoto T,Naka T

doi

10.1002/ibd.21384

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

491-502

issue

2

eissn

1078-0998

issn

1536-4844

journal_volume

17

pub_type

杂志文章
  • Higher Infliximab Levels Are Not Associated With an Increase in Adverse Events in Inflammatory Bowel Disease.

    abstract:Background:Patients requiring optimization of therapy for suboptimal response and/or targeting more robust outcomes may eventually reach high serum levels. Data evaluating the relationship between infliximab concentration and toxicity are limited. The aim of this study was to evaluate the frequency of adverse events (A...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izy066

    authors: Greener T,Kabakchiev B,Steinhart AH,Silverberg MS

    更新日期:2018-07-12 00:00:00

  • Inflammatory bowel disease and completed suicide in Danish adults.

    abstract:BACKGROUND:The risk of suicide is increased among people with inflammatory bowel disease (IBD); however, most of the evidence regarding this association comes from studies of all-cause mortality, with small numbers of people who have committed suicide, or from clinical case reports. The current study examined the assoc...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21298

    authors: Gradus JL,Qin P,Lincoln AK,Miller M,Lawler E,Sørensen HT,Lash TL

    更新日期:2010-12-01 00:00:00

  • Activation of the cannabinoid 2 receptor (CB2) protects against experimental colitis.

    abstract:BACKGROUND:Activation of cannabinoid (CB)(1) receptors results in attenuation of experimental colitis. Our aim was to examine the role of CB(2) receptors in experimental colitis using agonists (JWH133, AM1241) and an antagonist (AM630) in trinitrobenzene sulfonic acid (TNBS)-induced colitis in wildtype and CB(2) recept...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.20960

    authors: Storr MA,Keenan CM,Zhang H,Patel KD,Makriyannis A,Sharkey KA

    更新日期:2009-11-01 00:00:00

  • Fistulizing perianal Crohn's disease: contrast-enhanced magnetic resonance imaging assessment at 1 year on maintenance anti-TNF-alpha therapy.

    abstract:BACKGROUND:The aim of the study was to assess perianal fistulas by magnetic resonance imaging (MRI) in patients with severe fistulizing Crohn's disease (CD) using maintenance antitumor necrosis factor alpha (TNF-α) therapy and to correlate MRI changes with clinical outcome. METHODS:Perineal MRI before and after a 1-ye...

    journal_title:Inflammatory bowel diseases

    pub_type: 临床试验,杂志文章

    doi:10.1002/ibd.21568

    authors: Savoye-Collet C,Savoye G,Koning E,Dacher JN,Lerebours E

    更新日期:2011-08-01 00:00:00

  • Genetic and environmental context determines the course of colitis developing in IL-10-deficient mice.

    abstract::This review summarizes how interleukin-10 (IL-10)-deficient mice have permitted new insight into the complex interaction between genes and environment underlying pathogenesis of inflammatory bowel disease (IBD). The C57BL/6J strain develops only mild typhlocolitis in response to IL-10 deficiency. In contrast, C3H/HeJB...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1097/00054725-200209000-00006

    authors: Mähler M,Leiter EH

    更新日期:2002-09-01 00:00:00

  • Serum adalimumab concentration and clinical remission in patients with Crohn's disease.

    abstract:BACKGROUND:Drug concentration monitoring may be useful to guide therapeutic adjustments for anti-tumor necrosis factor agents in Crohn's disease. The relationship between serum adalimumab concentrations and clinical outcomes was assessed using data from CLinical Assessment of Adalimumab Safety and Efficacy Studied as I...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/MIB.0b013e3182813242

    authors: Chiu YL,Rubin DT,Vermeire S,Louis E,Robinson AM,Lomax KG,Pollack PF,Paulson SK

    更新日期:2013-05-01 00:00:00

  • Menstrual cycle changes in women with inflammatory bowel disease: a study from the ocean state Crohn's and colitis area registry.

    abstract:BACKGROUND:The effect of the inflammatory bowel diseases (IBD) on menstrual function is largely unknown. The aims of this study were to determine whether changes in menstrual function occur in the year before IBD diagnosis or in the initial years after diagnosis. METHODS:Women aged 18 years and older in the Ocean Stat...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/01.MIB.0000441347.94451.cf

    authors: Saha S,Zhao YQ,Shah SA,Esposti SD,Lidofsky S,Salih S,Bright R,Law M,Moniz H,Flowers N,Merrick M,Sands BE

    更新日期:2014-03-01 00:00:00

  • Mechanisms of natural tolerance in the intestine: implications for inflammatory bowel disease.

    abstract::Tolerance, the regulated inability to respond to a specific immunologic stimulant, is a physiological event important to normal immune function. Just as loss of tolerance to self-proteins results in autoimmune diseases, we assert that loss of tolerance to commensal flora in the intestinal lumen leads to inflammatory b...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1097/00054725-200407000-00023

    authors: Jump RL,Levine AD

    更新日期:2004-07-01 00:00:00

  • On the role of ischemia in the pathogenesis of IBD: a review.

    abstract::Inflammatory bowel disease (IBD) is a chronic intestinal disorder comprising 2 distinct but often overlapping diseases: Crohn's disease and ulcerative colitis. Although much research to identify the etiology of IBD has focused on genetic constitution, infectious causes, and immune dysregulation, its exact cause and pa...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1002/ibd.21061

    authors: Ibrahim CB,Aroniadis OC,Brandt LJ

    更新日期:2010-04-01 00:00:00

  • Risk Factors and Clinical Outcomes Associated with Cytomegalovirus Colitis in Patients with Acute Severe Ulcerative Colitis.

    abstract:BACKGROUND:Cytomegalovirus (CMV) colitis can contribute to an unfavorable outcome of acute severe ulcerative colitis (ASUC). The purpose of this study was to evaluate the clinical outcomes of ASUC according to the CMV status and identify risk factors for CMV colitis in patients with ASUC. METHODS:We retrospectively an...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000675

    authors: Lee HS,Park SH,Kim SH,Kim J,Choi J,Lee HJ,Kim WS,Lee JM,Kwak MS,Hwang SW,Yang DH,Kim KJ,Ye BD,Byeon JS,Myung SJ,Yoon YS,Yu CS,Kim JH,Yang SK

    更新日期:2016-04-01 00:00:00

  • Pericarditis complicating ulcerative colitis.

    abstract::: Pericarditis occurs rarely in association with inflammatory bowel disease. Because life-threatening complications may occur, pericarditis should be suspected in patients who present with chest symptoms. We report the case of a 28-year-old patient with ulcerative colitis who presented with pericarditis during an acti...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:

    authors: Hinterreiter M,Allinger S,Punzengruber C,Knoflach P

    更新日期:1995-10-01 00:00:00

  • Probing the Association of Pancreatitis in Inflammatory Bowel Disease.

    abstract::Inflammatory bowel disease (IBD) has been increasingly diagnosed in children and adults. Similarly, acute and chronic pancreatitis are increasingly prevalent conditions with potentially devastating consequences. There is a growing body of literature linking these 2 conditions. The purpose of this review is to provide ...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1097/MIB.0000000000000611

    authors: Srinath AI,Gupta N,Husain SZ

    更新日期:2016-02-01 00:00:00

  • Cell Trafficking Interference in Inflammatory Bowel Disease: Therapeutic Interventions Based on Basic Pathogenesis Concepts.

    abstract::After 20 years of successful targeting of pro-inflammatory cytokines for the treatment of IBD, an alternative therapeutic strategy has emerged, based on several decades of advances in understanding the pathogenesis of IBD. The targeting of molecules involved in leukocyte traffic has recently become a safe and effectiv...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1093/ibd/izy269

    authors: Pérez-Jeldres T,Tyler CJ,Boyer JD,Karuppuchamy T,Bamias G,Dulai PS,Boland BS,Sandborn WJ,Patel DR,Rivera-Nieves J

    更新日期:2019-01-10 00:00:00

  • The implications of acute pouchitis on the long-term functional results after restorative proctocolectomy.

    abstract::A prospective study was conducted to determine the implications of acute pouchitis on the long-term functional results of restorative proctocolectomy with J-pouch ileoanal anastomosis (IPAA). Between July 1988 and June 1996, 137 consecutive patients underwent IPAA for treatment of ulcerative colitis. 127 patients (93%...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.3780040405

    authors: Hurst RD,Chung TP,Rubin M,Michelassi F

    更新日期:1998-11-01 00:00:00

  • The case for using 5-aminosalicyclates in Crohn's disease: pro.

    abstract::Mesalamine has a well-established role in the management of ulcerative colitis. However, its role in the management of Crohn's disease (CD) is less clear. Studies evaluating its therapeutic value in CD have produced both positive and negative results. Meta-analyses have not clarified the situation, possibly because th...

    journal_title:Inflammatory bowel diseases

    pub_type: 评论,社论

    doi:10.1097/01.mib.0000160743.24772.69

    authors: Hanauer SB

    更新日期:2005-06-01 00:00:00

  • Therapeutic strategies for the management of ulcerative colitis.

    abstract::Induction and maintenance of remission, mucosal healing, the avoidance of surgical intervention, and decreasing the likelihood of cancer developing are the primary therapeutic goals in ulcerative colitis (UC). For the traditional therapies, 5-aminosalicylic acid (including mesalamine), corticosteroids, and thiopurines...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1002/ibd.20797

    authors: Ng SC,Kamm MA

    更新日期:2009-06-01 00:00:00

  • Bacterial Mucosa-associated Microbiome in Inflamed and Proximal Noninflamed Ileum of Patients With Crohn's Disease.

    abstract:BACKGROUND:Microbiota is most likely essential in the pathogenesis of Crohn's disease (CD). Fecal diversion after ileocecal resection (ICR) protects against CD recurrence, whereas infusion of fecal content triggers inflammation. After ICR, the majority of patients experience endoscopic recurrence in the neoterminal ile...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izaa107

    authors: Olaisen M,Flatberg A,Granlund AVB,Røyset ES,Martinsen TC,Sandvik AK,Fossmark R

    更新日期:2021-01-01 00:00:00

  • Crohn's is not a 6-week disease: lifelong management of mild to moderate Crohn's disease.

    abstract::Crohn's disease is an idiopathic, chronic inflammatory disorder of the digestive tract with heterogeneous clinical presentations. Crohn's is currently not a curable disease, and patients are faced with a lifetime of recurrent disease flare-ups and remissions. Management strategies for Crohn's must therefore be targete...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1097/00054725-200407002-00002

    authors: Lichtenstein GR,Hanauer SB,Kane SV,Present DH

    更新日期:2004-07-01 00:00:00

  • Unique dietary-related mouse model of colitis.

    abstract:BACKGROUND:A high-fat diet is a risk factor for the development of inflammatory bowel disease (IBD) in humans. Deoxycholate (DOC) is increased in the colonic contents in response to a high-fat diet. Thus, an elevated level of DOC in the colonic lumen may play a role in the natural course of development of IBD. METHODS...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/01.MIB.0000209789.14114.63

    authors: Bernstein H,Holubec H,Bernstein C,Ignatenko N,Gerner E,Dvorak K,Besselsen D,Ramsey L,Dall'Agnol M,Blohm-Mangone KA,Padilla-Torres J,Cui H,Garewal H,Payne CM

    更新日期:2006-04-01 00:00:00

  • Chemoprophylaxis of colorectal cancer in inflammatory bowel disease: current concepts.

    abstract::Ulcerative colitis and Crohn's disease both confer an increased risk of developing colorectal cancer. The use of 5-aminosalicylate as a remission-inducing agent has been long accepted. Its use as a potential chemoprophylactic agent has been proposed and is used by some practitioners. This review examines the most rece...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1002/ibd.20186

    authors: Levine JS,Burakoff R

    更新日期:2007-10-01 00:00:00

  • Enteric Infection in Relapse of Inflammatory Bowel Disease: The Utility of Stool Microbial PCR Testing.

    abstract:BACKGROUND:The similar presentations in relapse of inflammatory bowel disease (IBD) and enteric infection pose substantial barriers to diagnosis and treatment. The objective of this study was to investigate the incidence, etiology, predictors, and treatment of enteric infection in patients with IBD. METHODS:We reviewe...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000001097

    authors: Axelrad JE,Joelson A,Nobel YR,Lawlor G,Green PHR,Lichtiger S,Lebwohl B

    更新日期:2017-06-01 00:00:00

  • Antimicrobial peptide response to blood translocation of bacterial DNA in Crohn's disease is affected by NOD2/CARD15 genotype.

    abstract:BACKGROUND:Blood translocation of bacterial-DNA has been described in patients with Crohn's disease (CD). The host's immune cell types cooperate to respond against bacterial insults. Some antimicrobial peptides are inducible after culture with bacterial products and a linkage has been established between them and NOD2/...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.21537

    authors: Gutiérrez A,Holler E,Zapater P,Sempere L,Jover R,Pérez-Mateo M,Schoelmerich J,Such J,Wiest R,Francés R

    更新日期:2011-08-01 00:00:00

  • A Critical Role for Monocytes/Macrophages During Intestinal Inflammation-associated Lymphangiogenesis.

    abstract:BACKGROUND:Inflammation-associated lymphangiogenesis (IAL) is frequently observed in inflammatory bowel diseases. IAL is believed to limit inflammation by enhancing fluid and immune cell clearance. Although monocytes/macrophages (MΦ) are known to contribute to intestinal pathology in inflammatory bowel disease, their r...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1097/MIB.0000000000000731

    authors: Becker F,Kurmaeva E,Gavins FN,Stevenson EV,Navratil AR,Jin L,Tsunoda I,Orr AW,Alexander JS,Ostanin DV

    更新日期:2016-06-01 00:00:00

  • Fulminant Crohn's colitis: when only an antibody will do.

    abstract:BACKGROUND:Fulminant Crohn's colitis complicated by toxic dilatation of the large bowel usually requires surgery, which carries a substantial morbidity and mortality rate. METHODS:We report the case of a female with steroid refractory fulminant Crohn's colitis complicated by toxic megacolon who was successfully treate...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1002/ibd.20139

    authors: Ng SC,Kamm MA

    更新日期:2007-08-01 00:00:00

  • The Natural History, Treatments, and Outcomes of Portal Vein Thrombosis in Patients With Inflammatory Bowel Disease.

    abstract:BACKGROUND:Portal vein thrombosis (PVT) is a poorly described complication of inflammatory bowel disease (IBD). We sought to better characterize presentations, compare treatments, and assess outcomes in IBD-related PVT. METHODS:We conducted a retrospective investigation of IBD-related PVT at our institution. Multivari...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章

    doi:10.1093/ibd/izaa053

    authors: Naymagon L,Tremblay D,Zubizarreta N,Moshier E,Naymagon S,Mascarenhas J,Schiano T

    更新日期:2021-01-19 00:00:00

  • Elevated IL-13Ralpha2 in intestinal epithelial cells from ulcerative colitis or colorectal cancer initiates MAPK pathway.

    abstract:BACKGROUND:Chronic inflammation in ulcerative colitis (UC) is a sizeable risk factor for colorectal cancer (CRC). Interleukin-13 (IL-13) is elevated in the UC mucosa and may induce dysregulated signaling in neighboring intestinal epithelial cells (IECs) and thus function as a tumorogenic cytokine. METHODS:Expression o...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,收录出版

    doi:10.1002/ibd.21133

    authors: Mandal D,Levine AD

    更新日期:2010-05-01 00:00:00

  • Dilation of colonic strictures by intralesional injection of infliximab in patients with Crohn's colitis.

    abstract:BACKGROUND:Intestinal stenosis is a frequent complication of Crohn's disease, often leading to repeated bowel obstruction and surgery. The prevalence of small bowel stenosis has ranged from 20% to 40% and from 7% to 15% in patients with colonic disease. Although balloon dilation is the initial preferred approach, many ...

    journal_title:Inflammatory bowel diseases

    pub_type: 临床试验,杂志文章,评审

    doi:10.1002/ibd.20318

    authors: Swaminath A,Lichtiger S

    更新日期:2008-02-01 00:00:00

  • MicroRNAs in inflammatory bowel diseases: paradoxes and possibilities.

    abstract::MicroRNAs (miRNAs) are single-stranded RNA molecules, which influence the translation of messenger RNA and hence protein synthesis. The altered expression of miRNAs in disease states in cancer and autoimmune diseases including inflammatory bowel disease is providing new insights into disease pathogenesis. This underst...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,评审

    doi:10.1097/MIB.0000000000000288

    authors: Whiteoak SR,Felwick R,Sanchez-Elsner T,Fraser Cummings JR

    更新日期:2015-05-01 00:00:00

  • Multi-Center Experience of Vedolizumab Effectiveness in Pediatric Inflammatory Bowel Disease.

    abstract:BACKGROUND:Though vedolizumab has received regulatory approval for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) in adults, there is increasing off-label use in children. AIMS:To describe the experience with vedolizumab in pediatric inflammatory bowel disease (IBD) patients at 3 tertiary IBD center...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1097/MIB.0000000000000865

    authors: Singh N,Rabizadeh S,Jossen J,Pittman N,Check M,Hashemi G,Phan BL,Hyams JS,Dubinsky MC

    更新日期:2016-09-01 00:00:00

  • Biomarker-Based Models Outperform Patient-Reported Scores in Predicting Endoscopic Inflammatory Disease Activity.

    abstract:Background:The Crohn's Disease Activity Index (CDAI), a scoring index including patient-reported outcomes (PROs), has known limitations for measuring intestinal inflammatory disease burden. Noninvasive markers of inflammation could prove more accurate than PROs; thus, regulatory authorities are exploring the use of PRO...

    journal_title:Inflammatory bowel diseases

    pub_type: 杂志文章,多中心研究

    doi:10.1093/ibd/izx018

    authors: Morris MW,Stewart SA,Heisler C,Sandborn WJ,Loftus EV,Zello GA,Fowler SA,Jones JL

    更新日期:2018-01-18 00:00:00