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Why interleukin-10 supplementation does not work in Crohn's disease patients

World Journal of Gastroenterology 2013年第25期19卷 3931-3941页

作者： Gareth J Marlow Dominique van Gent Lynnette R Ferguson Discipline of Nutrition Faculty of Medical and Health Sciences The University of Auckland Auckland 1142 New Zealand Gareth J Marlow Lynnette R Ferguson Nutrigenomics New Zealand The University of Auckland

Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) or ulcerative colitis are chronic intestina disorders, which are on the increase in "Westernised" countries. IBD can be caused by both genetic and environmental factors. interleukin-10 (IL-10) is an immunoregulatory cytokine that has been identified as being involved in several diseases including IBD. Studies have shown that polymorphisms in the promoter region reduce serum levels of IL-10 and this reduction has been associated with some forms of IBD. Mouse models have shown promising results with IL-10 supplementation, as such IL-10 supplementation has been touted as being a possible alternative treatment for CD in humans. Clinical trials have shown that recombinant human IL-10 is safe and well tolerated up to a dose o 8 μg/kg. However, to date, the results of the clinica trials have been disappointing. Although CD activity was reduced as measured by the CD activity index IL-10 supplementation did not result in significantly reduced remission rates or clinical improvements when compared to placebo. This review discusses why IL-10supplementation is not effective in CD patients currently and what can be addressed to potentially make IL-10 supplementation a more viable treatment option in the future. Based on the current research we conclude that IL-10 supplementation is not a one size fits all treatment and if the correct population of patients is chosen then IL-10 supplementation could be of benefit.

关键词： Inflammatory bowel disease Crohn’s disease interleukin-10 Recombinant human interleukin-10

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Pyruvate dehydrogenase kinase is a negative regulator of interleukin-10 production in macrophages

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Journal of Molecular Cell Biology 2020年第7期12卷 543-555页

作者： Yi Rang Na Daun Jung Juha Song Jong-Wan Park Jung Joo Hong Seung Hyeok Seok Macrophage Lab Department of Microbiology and Immunology and Institute of Endemic DiseaseSeoul National University College of MedicineChongno-guSeoul 03080Republic of Korea Department of Biomedical Science BK21-Plus Education ProgramSeoul National University College ofMedicineJongno-guSeoul 03080Republic of Korea Department of Pharmacology Seoul National University College of MedicineJongno-guSeoul 03080Republic of Korea Cancer Research Institute and Ischemic/Hypoxic Disease Institute Seoul National University College ofMedicineJongno-guSeoul 03080Republic of Korea National Primate Research Center Korea Research Institute of Bioscience and BiotechnologyCheongju 28116Republic of Korea

interleukin-10(IL-10)is the most potent anti-inflammatory cytokine in the body and plays an essential role in determining outcomes of many inflammatory *** metabolism is a critical determinant of immune cell function;however,it is currently unclear whether metabolic processes are specifically involved in IL-10 *** this study,we aimed to find the central metabolic molecule regulating IL-10 production of macrophages,which are the main producers of *** analysis identified that metabolic changes were predominantly enriched in Kupffer cells at the early inflammatory phase of a mouse endotoxemia *** them,pyruvate dehydrogenase kinase(PDK)-dependent acute glycolysis was negatively involved in IL-10 *** or knockdown of PDK selectively increased macrophage IL-10 ***,PDK inhibition increased IL-10 production via profound phosphorylation of adenosine monophosphate(AMP)-activated protein kinase alpha 1(AMPKα1)by restricting glucose uptake in lipopolysaccharide-stimulated ***α1 consequently activated p38 mitogen-activated protein kinase,c-Jun N-terminal kinase,and cyclic AMP-responsive element-binding protein to regulate IL-10 *** study uncovers a previously unknown regulatory mechanism of IL-10 in activated macrophages involving an immunometabolic function of PDK.

关键词： macrophage pyruvate dehydrogenase kinase AMP-activated protein kinase interleukin-10

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Dietary supplementation of sulfur amino acids improves intestinal immunity to Eimeria in broilers treated with anti-interleukin-10 antibody

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Animal Nutrition 2022年第3期10卷 382-389页

作者： Zhouzheng Ren Jiakun Yan Rose Whelan Xujie Liao Daniel E.Bütz Maria K.Arendt Mark E.Cook Xiaojun Yang Thomas D.Crenshaw College of Animal Science and Technology Northwest A&F UniversityYanglingShaanxiChina Department of Animal Sciences University of WisconsinMadisonWIUSA Evonik Operations GmbH Hanau-WolfgangGermany

Oral antibody to interleukin-10(anti-IL-10)enhances the intestinal immune defense against *** sulfur amino acids methionine and cysteine(MtC)play essential roles in inducing and maintaining protective immune responses during intestinal ***,increased dietary MtC may support the anti-IL-10-induced intestinal immunity to ***(n=640)were arranged in a 2×2×2 factorial design with 2 levels of each of the 3 main factors:dietary standardized ileal digestible(SID)MtC levels(0.6%or 0.8%),dietary anti-IL-10 supplementation(with or without),and coccidiosis challenge(control or challenge).Briefly,the broilers were supplied with either 0.6%or 0.8%SID MtC,each with or without anti-IL-10(300 mg/kg),from d 10 to *** d 14,broilers from each diet were gavaged with either PBS or *** resulting Eimeria infection induced fecal oocyst shedding and intestinal *** fed 0.8%SID MtC(main effects,P≤0.05)had decreased feed-to-gain ratio,increased duodenum and cecum luminal anti-Eimeria IgA titers,and decreased fecal oocyst counts,when compared to 0.6%SID *** supplementation of anti-IL-10(main effects,P≤0.05)increased cecum luminal total IgA concentration and decreased cecum ***(P≤0.05)were detected for growth performance and cecum luminal IFN-γ.Briefly,the highest body weight gain and feed intake were reached in PBS-gavaged broilers fed 0.8%SID MtC with no anti-IL-10 and in Eimeria-challenged broilers fed 0.8%SID MtC with *** Eimeria-infected broilers,anti-IL-10 increased intestinal luminal IFN-γ and body weight gain only at 0.8%SID ***,anti-IL-10 increased intestinal luminal IFN-γ levels,decreased cecum lesions and restored growth only when fed with adequate amounts of sulfur amino *** findings underscore the importance of providing sufficient essential nutrients to support the anti-IL-10 induced immunity against coccidiosis.

关键词： Chicken Coccidiosis Egg yolk antibody interleukin-10 Sulfur amino acid

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interleukin-10 promoter polymorphisms in patients with hepatitis B virus infection or hepatocellular carcinoma in Chinese Han ethnic population

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Hepatobiliary & Pancreatic Diseases International 2006年第1期5卷 60-64页

作者： Juan Wang, Hong Ni, Li Chen and Wen-Qin Song College of Life Sciences, Nankai Umversity, Tianjin 300071. China and College of Life Sciences, Shenzhen University, Shenzhen 518060, China College of Life Sciences Nankai University Tianjin 300071 China.

BACKGROUND: Since single nucleotide polymorphisms (SNPs) can serve as gene markers, polymorphism profiles may help scientists to identify the full collection of genes that contribute to the development of complex diseases such as cancer. The distribution of interleukin-10 (IL-10) promoter polymorphisms in Chinese Han ethnic patients with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) was investigated in this study. METHODS: The polymorphisms of IL-10 promoter region were detected by pulymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing. Sixty-six health controls, 42 patients with HBV infection, 30 HCC patients, and cell line SMMC-7721 were examined this way. RESULTS: Polyrnorphisms of T/C or T/N on-872 site occurred frequently in Han ethnic population. Pulyrnorphisms were detected in HBV and HCC patients and cell line SMMC-7721. The hotspot among the pulymorphisms was inserting base A between-1058 and-1057. CONCLUSION: Polymorphisms of IL-10 promoter in HBV and HCC patients may be associated with HBV infection and HCC development.

关键词： interleukin-10 polymorphisms on promoter region polymerase chain reaction-single strand conformation polymorphism hepatitis B virus carcinoma, hepatocellular

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Metabolic syndrome attenuates ulcerative colitis: Correlation with interleukin-10 and galectin-3 expression

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World Journal of Gastroenterology 2019年第43期25卷 6465-6482页

作者： Marina Jovanovic Bojana Simovic Markovic Nevena Gajovic Milena Jurisevic Aleksandar Djukic Ivan Jovanovic Nebojsa Arsenijevic Aleksandra Lukic Natasa Zdravkovic Department of Internal Medicine Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Center for Molecular Medicine and Stem Cell Research Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of Pharmacy Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of Pathophysiology Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of Dentistry Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia

BACKGROUND Ulcerative colitis(UC)is a chronic disease characterized by inflammation of intestinal epithelium,primarily of the *** increasing prevalence of metabolic syndrome(MetS)in patients with UC has been documented ***,there is no evidence that MetS alters the course of the *** To test the influence of the MetS on the severity of UC and the local and systemic immune *** Eighty nine patients with de novo histologically confirmed UC were divided in two groups,according to ATP III criteria:Group without MetS(no MetS)and group with *** Clinically and histologically milder disease with higher serum level of immunosuppressive cytokine interleukin-10(IL-10)and fecal content of Galectin-3(Gal-3)was observed in subjects with UC and MetS,compared to subjects suffering from UC *** was accompanied with predomination of IL-10 over pro-inflammatory cytokines tumor necrosis factorα(TNF-α),interleukin-6(IL-6),and interleukin-17(IL-17)in the sera as well as Gal-3 over TNF-αand IL-17 in feces of UC patients with ***,the patients with both conditions(UC and MetS)had higher percentage of IL-10 producing and Gal-3 expressing innate and acquired immune cells in lamina *** Local dominance of Gal-3 and IL-10 over pro-inflammatory mediators in patients with MetS may present a mechanism for limiting the inflammatory process and subsequent tissue damage in UC.

关键词： Ulcerative colitis Metabolic syndrome Galectin-3 Inflammation interleukin-10 Systemic immune response

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Genetic association and epistatic interaction of the interleukin-10 signaling pathway in pediatric inflammatory bowel disease

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World Journal of Gastroenterology 2017年第27期23卷 4897-4909页

作者： Zhenwu Lin Zhong Wang John P Hegarty Tony R Lin Yunhua Wang Sue Deiling Rongling Wu Neal J Thomas Joanna Floros CHILD Research Department of Pediatricsthe Pennsylvania State UniversityCollege of Medicine Department of Radiology University of Pennsylvania Perelman School of Medicine Division of Biostatistics Department of Public Health Sciencethe Pennsylvania State UniversityCollege of Medicine Department of Surgery the Pennsylvania State UniversityCollege of Medicine Department of Obstetrics and Gynecology the Pennsylvania State UniversityCollege of Medicine

To study the genetic association and epistatic interaction of the interleukin (IL)-10 and IL-10/STAT3 pathways in pediatric inflammatory bowel disease (IBD). METHODSA total of 159 pediatric inflammatory IBD patients (Crohn’s disease, n = 136; ulcerative colitis, n = 23) and 129 matched controls were studied for genetic association of selected single nucleotide polymorphisms (SNPs) of the IL-10 gene and the genes IL10RA, IL10RB, STAT3, and HO1, from the IL-10/STAT3 signaling pathway. As interactions between SNPs from different loci may significantly affect the associated risk for disease, additive (a) and dominant (d) modeling of SNP interactions was also performed to examine high-order epistasis between combinations of the individual SNPs. RESULTSThe results showed that IL-10 rs304496 was associated with pediatric IBD (P = 0.022), but no association was found for two other IL-10 SNPs, rs1800872 and rs2034498, or for SNPs in genes IL10RA, IL10RB, STAT3, and HO1. However, analysis of epistatic interaction among these genes showed significant interactions: (1) between two IL-10 SNPs rs1800872 and rs3024496 (additive-additive P = 0.00015, Bonferroni P value (Bp) = 0.003); (2) between IL-10RB rs2834167 and HO1 rs2071746 (dominant-additive, P = 0.0018, Bp = 0.039); and (3) among IL-10 rs1800872, IL10RB rs2834167, and HO1 rs2071746 (additive-dominant-additive, P = 0.00015, Bp = 0.005), as well as weak interactions among IL-10 rs1800872, IL-10 rs3024496, and IL-10RA (additive-additive-additive, P = 0.003; Bp = 0.099), and among IL10RA, IL10RB, and HO1 genes (additive-dominant-additive, P = 0.008, Bp = 0.287). CONCLUSIONThese results indicate that both the IL-10 gene itself, and through epistatic interaction with genes within the IL-10/STAT3 signaling pathway, contribute to the risk of pediatric IBD.

关键词： Pediatric inflammatory bowel disease interleukin-10 HO1 Single nucleotide polymorphism IL10-STAT3 pathway Epistatic interaction

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Association of interleukin-10 polymorphisms with risk of irritable bowel syndrome:A meta-analysis

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World Journal of Gastroenterology 2013年第48期19卷 9472-9480页

作者： Shan-Yu Qin Hai-Xing Jiang Dong-Hong Lu You Zhou Department of Gastroenterology the First Affiliated Hospital of Guangxi Medical University Minerva Foundation Institute for Medical Research FI-00290 Helsinki Finland

AIM:To clarify the current understanding of the association between interleukin-10(IL-10)polymorphisms and the risk of irritable bowel syndrome(IBS).METHODS:We searched for studies in any language recorded in PubMed,Embase and Cochrane library before August *** associations under allele contrast model,codominant model,dominant model,and recessive model were *** strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios(OR)with 95%confidence interval(CI).Fixed effects model was used to pool the result if the test of heterogeneity was not significant,otherwise the random-effect model was ***:Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870(-1082 A/G),rs1800871(-819C/T),and rs1800872(-592A/C)of the IL-10 gene,which involved 928 cases and 1363 controls,were eligible for our *** results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS(GG+GA vs AA:OR=0.80,95%CI:0.66-0.96),(AA+GA vs GG:OR=0.68,95%CI:0.52-0.90).Subgroup analysis revealed such association only existed in Caucasian ethnicity(AA+GA vs GG,OR=0.70,95%CI:0.55-0.89).The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity(CC vs GG:OR=1.29,95%CI:1.01-1.16).There were no associations between rs1800871 polymorphisms and the IBS ***:The results suggest that IL-10 rs1800870confers susceptibility to the risk of IBS in Caucasian ethnicity,and the rs1800872 may associate with IBS risk in ***,no significant associations are found between rs1800871 and IBS risk.

关键词： interleukin-10 Irritable bowel syndrome Gene polymorphism Case-control Meta-analysis

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Research advances of vasoactive intestinal peptide in the pathogenesis of ulcerative colitis by regulating interleukin-10 expression in regulatory B cells

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World Journal of Gastroenterology 2020年第48期26卷 7593-7602页

作者： Xiong Sun Yao Huang Ya-Li Zhang Dan Qiao Yan-Cheng Dai Department of Gastroenterology Shanghai PuTuo District People's Hospital Affiliated to Tongji UniversityTongji University School of MedicineShanghai 200060China Department of Digestive Diseases Jing'an District Central HospitalFudan UniversityShanghai 200040China Institute of Digestive Diseases LongHua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of Gastroenterology Shanghai Traditional Chinese Medicine Integrated HospitalShanghai University of Traditional Chinese MedicineShanghai 200082China

Ulcerative colitis(UC)is a chronic relapsed intestinal disease with an increasing incidence around the *** pathophysiology of UC remains ***,the role of the interaction between the enteric nervous system and the immune system in the pathogenesis of UC has been the focus of attention and has become a research *** intestinal peptide(VIP)is a kind of endogenous neuropeptide with regulatory activity on intestinal *** has been shown to regulate immune disorders in animal and human experiments and has become an effective anti-inflammatory and immune modulator that affects the innate immune system and adaptive immune *** B cells(Bregs)are a new group of B cells that negatively regulate the immunity and have received extensive attention in immune *** can regulate immune tolerance by producing interleukin(IL)-10,IL-35,and transforming growth factor-β,suppressing autoimmune diseases or excessive inflammatory *** secretion of IL-10 by Bregs induces the development of T helper(Th)0 and Th2 *** also induces Th2 cytokines and inhibits Th1 cytokines,thereby inhibiting Th1 cells and the Th1/Th2 *** further clarity on the mechanism of the regulation of IL-10 expression by VIP in Bregs in colitis patients,we believe that Bregs can provide a novel strategy for the clinical treatment of ***,we aim to review the current literature on this evolving topic.

关键词： Vasoactive intestinal peptide Ulcerative colitis interleukin-10 Bregs Pathogenesis

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Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice

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World Journal of Gastroenterology 2014年第27期20卷 9106-9115页

作者： Hanying Zhang Yansong Xue Hui Wang Yan Huang Min Du Qiyuan Yang Mei-Jun Zhu School of Food Science Washington State University Department of Animal Science University of Wyoming Department of Animal Science Washington State University

AIM: To test the role of mast cells in gut inflammation and colitis using interleukin (IL)-10-deficient mice as an experimental model.

关键词： Colitis interleukin-10 Inflammation Inflammatory bowel disease Mast cells Mice

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Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

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World Journal of Stem Cells 2024年第5期16卷 560-574页

作者： Meng-Hao Lyu Ce Bian Yi-Ping Dou Kang Gao Jun-Ji Xu Pan Ma Department of Periodontics School of StomatologyCapital Medical UniversityBeijing 100050China Department of Orthodontics School of StomatologyCapital Medical UniversityBeijing 100050China Department of Dental Implantology School of StomatologyCapital Medical UniversityBeijing 100050China Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction School of StomatologyCapital Medical UniversityBeijing 100050China Beijing Laboratory of Oral Health Capital Medical UniversityBeijing 100050China

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be *** the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair *** To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory *** IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory *** this study,we investigated its impact on the proliferation,migration,and osteogenesis of *** expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated ***,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 *** IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of ***,STAT3 signaling plays a crucial role in the process by which IL-10 influences ***,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of *** Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of *** IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

关键词： Macrophages interleukin-10 Bone marrow mesenchymal stem cells Signal transducer and activator of transcription 3 Inflammatory response

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