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Klekotka P, Lavoie L, Mitchell B, Iheanacho I, Burge R, Cohee A, Puckett J, Nirula A. Systematic literature review on early clinical evidence for immune-resolution therapies and potential benefits to patients and healthcare providers. Front Immunol 2024; 15:1425478. [PMID: 39483464 PMCID: PMC11524942 DOI: 10.3389/fimmu.2024.1425478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 09/13/2024] [Indexed: 11/03/2024] Open
Abstract
Introduction Several current therapies for autoimmune diseases do not provide sustained remission. Therapies that focus on the restoration of homeostasis within the immune system (i.e., immune resolution) could overcome the limitations of current therapies and provide more durable remission. However, there is no established consensus on appropriate clinical trial designs and endpoints to evaluate such therapies. Therefore, we conducted a systematic literature review (SLR) focusing on five index diseases (asthma, atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus [SLE], and ulcerative colitis) to explore published literature on 1) expert opinion on immune-resolution outcomes that should be measured in clinical trials; and 2) quantification of immune resolution in previous clinical trials. Methods The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase and MEDLINE databases were systematically searched (2013-2023) for published English language articles. Conference proceedings (2020-2022) from American Academy of Dermatology, American College of Rheumatology, Digestive Disease Week, European Alliance of Associations for Rheumatology, and European Academy of Dermatology and Venereology were searched to include relevant abstracts. The study protocol was registered in PROSPERO (CRD42023406489). Results The SLR included 26 publications on 20 trials and 12 expert opinions. Expert opinions generally lacked specific recommendations on the assessment of immune resolution in clinical trials and instead suggested targets or biomarkers for future therapies. The targets included thymic stromal lymphopoietin (TSLP) in asthma; T helper (Th)2 and Th22 cells and their respective cytokines (interleukin [IL]-4R and IL-22) in atopic dermatitis; inhibitory/regulatory molecules involved in T-cell modulation, and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) in rheumatoid arthritis; low-dose IL-2 therapy in SLE; and pro-resolution mediators in ulcerative colitis and asthma. In the interventional studies, direct biomarker assessments of immune resolution were the number/proportion of regulatory T-cells (Treg) and the ratio Th17/Treg in SLE and rheumatoid arthritis; the number of T follicular helper cells (Tfh), Th1, Th2, Th17, and Th22 in atopic dermatitis, rheumatoid arthritis, and SLE; and mucosal proinflammatory gene signatures (tumor necrosis factor [TNF], interleukin 1 alpha [IL1A], regenerating family member 1 alpha [REG1A], IL8, interleukin 1 beta [IL1B], and leukocyte immunoglobulin-like receptors A [LILRA]) in ulcerative colitis. Several studies reported a statistically significant relationship between clinical remission and immune-resolution biomarkers, suggesting a link between T-cell homeostasis, cytokine production, and disease activity in autoimmune diseases. Discussion Existing literature does not offer clear guidance on the evaluation of immune resolution in interventional studies. Further research and consensus are needed to assess a treatment's ability to induce long-term remission or low disease activity. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023406489, identifier CRD42023406489.
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Affiliation(s)
- Paul Klekotka
- Eli Lilly and Company, Indianapolis, IN, United States
| | | | - Beth Mitchell
- Eli Lilly and Company, Indianapolis, IN, United States
| | | | - Russel Burge
- Eli Lilly and Company, Indianapolis, IN, United States
- Division of Pharmaceutical Sciences, Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, United States
| | - Andrea Cohee
- Eli Lilly and Company, Indianapolis, IN, United States
| | | | - Ajay Nirula
- Eli Lilly and Company, Indianapolis, IN, United States
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Lee S, Heo J, Ahn EK, Kim JH, Kim YH, Chang HK, Lee SJ, Kim J, Park SJ. Conditioned secretome of adipose-derived stem cells improves dextran sulfate sodium-induced colitis in mice. World J Gastroenterol 2021; 27:3342-3356. [PMID: 34163116 PMCID: PMC8218368 DOI: 10.3748/wjg.v27.i23.3342] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/05/2021] [Accepted: 05/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Inflammatory bowel diseases (IBD) is related to uncontrolled immune response. Currently, there is no successful treatment for significant improvement in IBD. Stem cells display their therapeutic effects through their repopulating capacity or secreting factors. AIM To investigate the effects of conditioned mouse adipose-derived stem cells (mADSCs) secretome on colitis-induced mice. METHODS mADSCs were isolated from adipose tissue of C57BL/6 mice. Conditioned mADSCs secrectome was obtained by culturing of mADSCs with lipopolysaccharides (LPS, 1 μg/mL) for 24 h. Acute colitis was induced by 2% dextran sulfate sodium (DSS) drinking water for 7 d and then normal drinking water for 4 d. The mice were treated with normal culture medium (NM group), conditioned mADSCs secretome (CM group) or mADSCs (SC group). The length of colon and histopatholgy of colon tissues were evaluated. The mRNA expression levels of inflammatory cytokines in colon tissue and the serum interleukin (IL)-6 levels were determined. RESULTS The isolated mADSCs maintained the mADSCs specific gene expression profiles during experiment. The conditioned mADSCs secretome released by the treatment of mADSCs with LPS contained mainly inflammatory chemokines, colony-stimulating factors and inflammatory cytokines. The loss of body weight and reduction in colon length were ameliorated in the CM group. The conditioned mADSCs secretome reduced the histological score in colon tissue. The expression of IL-1b and IL-6 mRNAs in colon tissues significantly inhibited in the CM group compared to SC group and NM group, respectively. The elevation of serum IL-6 levels was also ameliorated in the CM group. These results indicate that the conditioned mADSCs secretome suppressed the synthesis of inflammatory cytokines in damaged colon tissue and the elevation of serum IL-6 concentration in DSS-induced mice. CONCLUSION Conditioned mADSCs secretome might play regenerative roles by the suppression of IL-6 in serum and tissue during acute colitis, and may be more effective than stem cells themselves in the regeneration of colon tissue.
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Affiliation(s)
- Seunghun Lee
- Department of Colorectal Surgery, Kosin University College of Medicine, Busan 49267, South Korea
| | - Jeonghoon Heo
- Department of Molecular Biology and Immunology, Kosin University College of Medicine, Busan 49267, South Korea
| | - Eun-Kyung Ahn
- Department of Molecular Biology and Immunology, Kosin University College of Medicine, Busan 49267, South Korea
| | - Jae Hyun Kim
- Department of Gastroenterology, Kosin University College of Medicine, Busan 49267, South Korea
| | - Young-Ho Kim
- Department of Molecular Biology and Immunology, Kosin University College of Medicine, Busan 49267, South Korea
| | - Hee-Kyung Chang
- Department of Pathology, Kosin University College of Medicine, Busan 49267, South Korea
| | - Sang-Joon Lee
- Department of Ophthalmology, Kosin University College of Medicine, Busan 49267, South Korea
| | - Jongsik Kim
- Department of Anatomy, Kosin University College of Medicine, Busan 49267, South Korea
| | - Seun-Ja Park
- Department of Gastroenterology, Kosin University College of Medicine, Busan 49267, South Korea
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V S A, S K K. Phloretin Ameliorates Acetic Acid Induced Colitis Through Modulation of Immune and Inflammatory Reactions in Rats. Endocr Metab Immune Disord Drug Targets 2020; 21:163-172. [PMID: 32579511 DOI: 10.2174/1871530320666200624120257] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Revised: 03/16/2020] [Accepted: 05/11/2020] [Indexed: 01/30/2023]
Abstract
BACKGROUND Adverse effects associated with current therapy for Ulcerative colitis (UC) over prolonged treatment periods and the high relapse rate limit their use. Incorporating fruits as regular diet has beneficial role in the management of UC. Phloretin, a dihydrochalcone of apple is reported for its anti-oxidant and anti-inflammatory effects. Our study aims to evaluate the effectiveness of phloretin on experimentally induced ulcerative colitis in rats. METHODS In vitro study was performed using Raw 264.7 cells stimulated with LPS (1μg/mL) and in in-vivo study, colitis was induced by intra rectal administration of 4% Acetic acid. Phloretin (50 mg/kg) was given orally for 3 days to Wistar rats after induction for the post-treatment group and 1 day before induction to the pre-treatment group. Macroscopical, biochemical and histopathological evaluations were performed to assess the effectiveness. RESULTS A concentration dependent inhibition of MPO and iNOS activity was obtained in LPS stimulated neutrophil cells. Phloretin exerted ameliorative effect in both pre and post-treatment groups by restoring plasma ALP and LDH level and reduce inflammatory markers like myeloperoxidase, nitric oxide and eosinophil peroxidase level as well as downregulates colon ICAM-1 gene in acetic acid induced ulcerative colitis in rats. Antioxidative potency was confirmed by restoring tissue GSH level. Phloretin prevents mucosal damage and it was confirmed by histopathological analysis. CONCLUSION Collectively, our findings provide evidence that phloretin might be useful as a natural therapeutic agent in the management of UC as well as may pose a promising outcome for future clinical usage.
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Affiliation(s)
- Arya V S
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India
| | - Kanthlal S K
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India
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Alenazi Y, Singh K, Davies G, Eaton JRO, Elders P, Kawamura A, Bhattacharya S. Genetically engineered two-warhead evasins provide a method to achieve precision targeting of disease-relevant chemokine subsets. Sci Rep 2018; 8:6333. [PMID: 29679010 PMCID: PMC5910400 DOI: 10.1038/s41598-018-24568-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Accepted: 04/06/2018] [Indexed: 12/21/2022] Open
Abstract
Both CC and CXC-class chemokines drive inflammatory disease. Tick salivary chemokine-binding proteins (CKBPs), or evasins, specifically bind subsets of CC- or CXC-chemokines, and could precisely target disease-relevant chemokines. Here we have used yeast surface display to identify two tick evasins: a CC-CKBP, P1243 from Amblyomma americanum and a CXC-CKBP, P1156 from Ixodes ricinus. P1243 binds 11 CC-chemokines with Kd < 10 nM, and 10 CC-chemokines with Kd between 10 and 100 nM. P1156 binds two ELR + CXC-chemokines with Kd < 10 nM, and four ELR + CXC-chemokines with Kd between 10 and 100 nM. Both CKBPs neutralize chemokine activity with IC50 < 10 nM in cell migration assays. As both CC- and CXC-CKBP activities are desirable in a single agent, we have engineered "two-warhead" CKBPs to create single agents that bind and neutralize subsets of CC and CXC chemokines. These results show that tick evasins can be linked to create non-natural proteins that target subsets of CC and CXC chemokines. We suggest that "two-warhead" evasins, designed by matching the activities of parental evasins to CC and CXC chemokines expressed in disease, would achieve precision targeting of inflammatory disease-relevant chemokines by a single agent.
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Affiliation(s)
- Yara Alenazi
- RDM Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
| | - Kamayani Singh
- RDM Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
| | - Graham Davies
- RDM Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
| | - James R O Eaton
- RDM Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
- Department of Chemistry, University of Oxford, Oxford, United Kingdom
| | - Philip Elders
- RDM Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
| | - Akane Kawamura
- RDM Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
- Department of Chemistry, University of Oxford, Oxford, United Kingdom
| | - Shoumo Bhattacharya
- RDM Division of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom.
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Katsanos KH, Papadakis KA. Inflammatory Bowel Disease: Updates on Molecular Targets for Biologics. Gut Liver 2018; 11:455-463. [PMID: 28486793 PMCID: PMC5491079 DOI: 10.5009/gnl16308] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Revised: 08/03/2016] [Accepted: 08/03/2016] [Indexed: 12/13/2022] Open
Abstract
Therapy for inflammatory bowel disease (IBD) has changed, with several new agents being evaluated. The era of anti-tumor necrosis factor (anti-TNF) antibody therapy saw remarkable progress in IBD therapy. Some patients, however, do not respond to anti-TNF treatment, or their response decreases over time. This phenomenon highlights the need to identify new molecular targets for therapy in IBD. The targets of new therapeutic molecules in IBD must aim to restore immune dysregulation by the inhibition of proinflammatory cytokines (TNF-α, interleukin [IL]-6, IL-13, IL-17, IL-18, and IL-21) and augmentation of the effect of anti-inflammatory cytokines (IL-10, IL-11, and transforming growth factor β) and to pursue new anti-inflammatory targets, such as regulatory T-cell therapy, Smad7 antisense, Janus-activated kinase inhibition, Toll-like receptor stimulation, leukocyte adhesion, and blockade of T-cell homing via integrins and mucosal addressin cellular adhesion molecule-1. In addition, potential molecular targets could restore mucosal barrier function and stimulate mucosal healing. Despite these potential targets, the value and clinical significance of most new molecules remain unclear, and clinical efficacy and safety must be better defined before their implementation in clinical practice. This article aims to review the promising and emerging molecular targets that could be clinically meaningful for novel therapeutic approaches.
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Affiliation(s)
- Konstantinos H Katsanos
- Division of Gastroenterology, Department of Internal Medicine, University of Ioannina School of Health Sciences, Ioannina, Greece
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Fiocchi C. Inflammatory Bowel Disease: Complexity and Variability Need Integration. Front Med (Lausanne) 2018; 5:75. [PMID: 29619371 PMCID: PMC5873363 DOI: 10.3389/fmed.2018.00075] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 03/07/2018] [Indexed: 12/16/2022] Open
Affiliation(s)
- Claudio Fiocchi
- Department of Pathobiology, Lerner Research Institute, Cleveland, OH, United States.,Department of Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, United States
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Song JY, Kang HJ, Hong JS, Kim CJ, Shim JY, Lee CW, Choi J. Umbilical cord-derived mesenchymal stem cell extracts reduce colitis in mice by re-polarizing intestinal macrophages. Sci Rep 2017; 7:9412. [PMID: 28842625 PMCID: PMC5573412 DOI: 10.1038/s41598-017-09827-5] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 07/31/2017] [Indexed: 12/16/2022] Open
Abstract
Human umbilical cord mesenchymal stem cells (hUC-MSCs), originating in Wharton’s jelly, are multipotent stem cells that home to damaged tissues and can modulate the immune system. We examined whether administering extracts of MSCs (MSC-Ex) instead of MSCs could augment the beneficial effects of MSC therapy by overcoming the low homing efficiency of MSCs systemically administered in inflammatory bowel diseases (IBD). Dextran sodium sulfate-induced colitis model was established in C57BL/6 mice, and MSC-Ex was administered intraperitoneally. MSC-Ex reduced colitis, disease activity index (DAI), and histological colitis scores, and increased the body weight. Treatment with MSC-Ex completely blocked the induction of inflammatory cytokines, which were strongly detected in mice with colitis. MSC-Ex shifted the macrophage functional phenotype from M1 to M2 by decreasing the levels of MCP1, CXCL9, and iNOS, but increasing the levels of IL-10, LIGHT, CCL1, and Arg-1. MSC-Ex recovered the destruction of the epithelial barrier in the differentiated Caco-2 cells in vitro. Treatment with MSC-Ex was more potent than that with MSC in reducing DAI, the histological score, and nitrite levels. These data strongly support that MSC-Ex treatment can be a potent approach to overcome severe refractory IBD.
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Affiliation(s)
- Ji-Young Song
- Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Hyo Jeong Kang
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.,Department of Physiology, Asan-Minnesota Institute for Innovating Transplantation, Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Joon Seok Hong
- Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Gyeonggi-do, Korea
| | - Chong Jai Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jae-Yoon Shim
- Department Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Christopher W Lee
- Department of Molecular and Cellular Biology, University of California, Davis, Davis, California, USA
| | - Jene Choi
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
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Koh SJ, Choi Y, Kim BG, Lee KL, Kim DW, Kim JH, Kim JW, Kim JS. Matricellular Protein Periostin Mediates Intestinal Inflammation through the Activation of Nuclear Factor κB Signaling. PLoS One 2016; 11:e0149652. [PMID: 26890265 PMCID: PMC4758640 DOI: 10.1371/journal.pone.0149652] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Accepted: 02/03/2016] [Indexed: 01/04/2023] Open
Abstract
Periostin is a matricellular protein that interacts with various integrin molecules on the cell surface. Although periostin is expressed in inflamed colonic mucosa, its role in the regulation of intestinal inflammation remains unclear. We investigated the role of periostin in intestinal inflammation using Postn-deficient (Postn-/-) mice. Intestinal epithelial cells (IECs) were transfected by Postn small interfering RNAs. Periostin expression was determined in colon tissue samples from ulcerative colitis (UC) patients. Oral administration of dextran sulfate sodium (DSS) or rectal administration of trinitrobenzene sulfonic acid, induced severe colitis in wild-type mice, but not in Postn-/- mice. Administration of recombinant periostin induced colitis in Postn-/- mice. The periostin neutralizing-antibody ameliorated the severity of colitis in DSS-treated wild-type mice. Silencing of Postn inhibited inteleukin (IL)-8 mRNA expression and NF-κB DNA-binding activity in IECs. Tumor necrosis factor (TNF)-α upregulated mRNA expression of Postn in IECs, and recombinant periostin strongly enhanced IL-8 expression in combination with TNF-α, which was suppressed by an antibody against integrin αv (CD51). Periostin and CD51 were expressed at significantly higher levels in UC patients than in controls. Periostin mediates intestinal inflammation through the activation of NF-κB signaling, which suggests that periostin is a potential therapeutic target for inflammatory bowel disease.
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Affiliation(s)
- Seong-Joon Koh
- Department of Internal Medicine, Division of Gastroenterology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Younjeong Choi
- Department of Internal Medicine, Division of Gastroenterology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Byeong Gwan Kim
- Department of Internal Medicine, Division of Gastroenterology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kook Lae Lee
- Department of Internal Medicine, Division of Gastroenterology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Woo Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Ho Kim
- Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Won Kim
- Department of Internal Medicine, Division of Gastroenterology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
- * E-mail: (JSK); (JWK)
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- * E-mail: (JSK); (JWK)
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Martínez-Montiel MP, Casis-Herce B, Gómez-Gómez GJ, Masedo-González A, Yela-San Bernardino C, Piedracoba C, Castellano-Tortajada G. Pharmacologic therapy for inflammatory bowel disease refractory to steroids. Clin Exp Gastroenterol 2015; 8:257-69. [PMID: 26316792 PMCID: PMC4544729 DOI: 10.2147/ceg.s58152] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Although corticosteroids are an effective treatment for induction of remission in inflammatory bowel disease (IBD), many patients are dependent on or refractory to corticosteroids. This review is based on scrutinizing current literature with emphasis on randomized controlled trials, meta-analyses, and Cochrane reviews on the management of IBD refractory to corticosteroids. Based on this evidence, we propose algorithms and optimization strategies for use of immunomodulator and biologic therapy in IBD refractory to corticosteroids.
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Affiliation(s)
| | - B Casis-Herce
- Division of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain
| | - G J Gómez-Gómez
- Division of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain
| | | | | | - C Piedracoba
- Division of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain
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Mehta P, Furuta GT. Eosinophils in Gastrointestinal Disorders: Eosinophilic Gastrointestinal Diseases, Celiac Disease, Inflammatory Bowel Diseases, and Parasitic Infections. Immunol Allergy Clin North Am 2015. [PMID: 26209893 DOI: 10.1016/j.iac.2015.04.003] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The gastrointestinal (GI) tract provides an intriguing organ for considering the eosinophil's role in health and disease. The normal GI tract, except for the esophagus, is populated by eosinophils that are present throughout the mucosa, raising the possibility that eosinophils participate in innate mechanisms of defense. However, data from clinical studies associates increased numbers of eosinophils with inflammatory GI diseases, prompting concerns that eosinophils may have a deleterious effect on the gut. We present clinical features of 4 disease processes that have been associated with eosinophilia and suggest areas requiring investigation as to their clinical significance and scientific relevance.
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Affiliation(s)
- Pooja Mehta
- Department of Pediatrics, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 East 16th Ave B290, Aurora, CO 80045, USA
| | - Glenn T Furuta
- Department of Pediatrics, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 East 16th Ave B290, Aurora, CO 80045, USA.
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Tontini GE, Vecchi M, Pastorelli L, Neurath MF, Neumann H. Differential diagnosis in inflammatory bowel disease colitis: State of the art and future perspectives. World J Gastroenterol 2015; 21:21-46. [PMID: 25574078 PMCID: PMC4284336 DOI: 10.3748/wjg.v21.i1.21] [Citation(s) in RCA: 143] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 07/31/2014] [Accepted: 09/16/2014] [Indexed: 02/06/2023] Open
Abstract
Distinction between Crohn’s disease of the colon-rectum and ulcerative colitis or inflammatory bowel disease (IBD) type unclassified can be of pivotal importance for a tailored clinical management, as each entity often involves specific therapeutic strategies and prognosis. Nonetheless, no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations. Hence, we have performed a literature search to address the problem of differential diagnosis in IBD colitis, revised current and emerging diagnostic tools and refined disease classification strategies. Nowadays, the differential diagnosis is an untangled issue, and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis. This topic is receiving emerging attention, as medical therapies, surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients. The optimization of standard diagnostic approaches based on clinical features, biomarkers, radiology, endoscopy and histopathology appears to provide only marginal benefits. Conversely, emerging diagnostic techniques in the field of gastrointestinal endoscopy, molecular pathology, genetics, epigenetics, metabolomics and proteomics have already shown promising results. Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD, better reflecting diverse disease behaviors based on specific pathogenic pathways.
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