Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative ColitisSummary
Background & Aims: Inflammatory bowel diseases are multifactorial diseases commonly treated with either immunomodulatory drugs or anti–tumor necrosis factor (TNF). Currently, failure to respond to anti-TNF therapy (assessed no earlier than 8–12 weeks after starting treatment) occurs in 20%–4...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X22000522 |
| _version_ | 1818546917197479936 |
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| author | Marina Liso Giulio Verna Elisabetta Cavalcanti Stefania De Santis Raffaele Armentano Angela Tafaro Antonio Lippolis Pietro Campiglia Antonio Gasbarrini Mauro Mastronardi Theresa Torres Pizarro Fabio Cominelli Loris Riccardo Lopetuso Marcello Chieppa |
| author_facet | Marina Liso Giulio Verna Elisabetta Cavalcanti Stefania De Santis Raffaele Armentano Angela Tafaro Antonio Lippolis Pietro Campiglia Antonio Gasbarrini Mauro Mastronardi Theresa Torres Pizarro Fabio Cominelli Loris Riccardo Lopetuso Marcello Chieppa |
| author_sort | Marina Liso |
| collection | DOAJ |
| description | Background & Aims: Inflammatory bowel diseases are multifactorial diseases commonly treated with either immunomodulatory drugs or anti–tumor necrosis factor (TNF). Currently, failure to respond to anti-TNF therapy (assessed no earlier than 8–12 weeks after starting treatment) occurs in 20%–40% of patients enrolled in clinical trials and in 10%–20% in clinical practice. Murine models of inflammatory bowel disease provide important tools to better understand disease mechanism(s). In this context and among the numerous models available, Winnie–TNF–knockout (KO) mice recently were reported to show characteristics of ulcerative colitis (UC) that are independent of TNF, and with increased interleukin (IL)1β production. Methods: Herein, the efficacy of recombinant IL1-receptor antagonist (anakinra) administration was evaluated in Winnie-TNF-KO mice, used as a UC model of primary anti-TNF nonresponders. Results: We analyzed gut mucosal biopsy specimens and circulating cytokine profiles of a cohort of 30 UC patients; approximately 75% of primary nonresponders were characterized by abundant IL1β in both the serum and local intestinal tissues. In Winnie-TNF-KO mice, administration of anakinra efficiently reduced the histologic score of the distal colon, which represents the most common site of inflammation in Winnie mice. Furthermore, among lamina propria and mesenteric lymph node–derived T cells, interferon γ–expressing CD8+ T cells were reduced significantly after anakinra administration. Conclusions: Our study provides new insight and alternative approaches to treat UC patients, and points to anti-IL1 strategies (ie, anakinra) that may be a more effective therapeutic option for primary nonresponders to anti-TNF therapy. |
| first_indexed | 2024-12-12T07:59:38Z |
| format | Article |
| id | doaj.art-a95b569721e54df88b37d4e4016c05fe |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-12T07:59:38Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-a95b569721e54df88b37d4e4016c05fe2022-12-22T00:32:11ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2022-01-01141151171Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative ColitisSummaryMarina Liso0Giulio Verna1Elisabetta Cavalcanti2Stefania De Santis3Raffaele Armentano4Angela Tafaro5Antonio Lippolis6Pietro Campiglia7Antonio Gasbarrini8Mauro Mastronardi9Theresa Torres Pizarro10Fabio Cominelli11Loris Riccardo Lopetuso12Marcello Chieppa13National Institute of Gastroenterology “S. de Bellis,” Research Hospital, Castellana Grotte (BA), ItalyDepartment of Pharmacy, University of Salerno, Fisciano (SA), Italy; Digestive Health Research Institute, Case Western Reserve University School of Medicine, Cleveland, Ohio, USANational Institute of Gastroenterology “S. de Bellis,” Research Hospital, Castellana Grotte (BA), ItalyDepartment of Pharmacy-Drug Science, University of Bari Aldo Moro, Bari, ItalyNational Institute of Gastroenterology “S. de Bellis,” Research Hospital, Castellana Grotte (BA), ItalyNational Institute of Gastroenterology “S. de Bellis,” Research Hospital, Castellana Grotte (BA), ItalyNational Institute of Gastroenterology “S. de Bellis,” Research Hospital, Castellana Grotte (BA), ItalyDepartment of Pharmacy, University of Salerno, Fisciano (SA), ItalyDigestive Disease Center–Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Roma, ItalyNational Institute of Gastroenterology “S. de Bellis,” Research Hospital, Castellana Grotte (BA), ItalyDigestive Health Research Institute, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USADigestive Health Research Institute, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USADigestive Disease Center–Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Roma, Italy; Department of Medicine and Ageing Sciences, ''G. d'Annunzio'' University of Chieti-Pescara, Chieti, Italy; Center for Advanced Studies and Technology, “G. d'Annunzio” University of Chieti-Pescara, Chieti, ItalyNational Institute of Gastroenterology “S. de Bellis,” Research Hospital, Castellana Grotte (BA), Italy; Dietetics and Clinical Nutrition Laboratory, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy; Correspondence Address correspondence to: Marcello Chieppa, PhD, Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, via Monteroni, 73100 Lecce, Italy.Background & Aims: Inflammatory bowel diseases are multifactorial diseases commonly treated with either immunomodulatory drugs or anti–tumor necrosis factor (TNF). Currently, failure to respond to anti-TNF therapy (assessed no earlier than 8–12 weeks after starting treatment) occurs in 20%–40% of patients enrolled in clinical trials and in 10%–20% in clinical practice. Murine models of inflammatory bowel disease provide important tools to better understand disease mechanism(s). In this context and among the numerous models available, Winnie–TNF–knockout (KO) mice recently were reported to show characteristics of ulcerative colitis (UC) that are independent of TNF, and with increased interleukin (IL)1β production. Methods: Herein, the efficacy of recombinant IL1-receptor antagonist (anakinra) administration was evaluated in Winnie-TNF-KO mice, used as a UC model of primary anti-TNF nonresponders. Results: We analyzed gut mucosal biopsy specimens and circulating cytokine profiles of a cohort of 30 UC patients; approximately 75% of primary nonresponders were characterized by abundant IL1β in both the serum and local intestinal tissues. In Winnie-TNF-KO mice, administration of anakinra efficiently reduced the histologic score of the distal colon, which represents the most common site of inflammation in Winnie mice. Furthermore, among lamina propria and mesenteric lymph node–derived T cells, interferon γ–expressing CD8+ T cells were reduced significantly after anakinra administration. Conclusions: Our study provides new insight and alternative approaches to treat UC patients, and points to anti-IL1 strategies (ie, anakinra) that may be a more effective therapeutic option for primary nonresponders to anti-TNF therapy.http://www.sciencedirect.com/science/article/pii/S2352345X22000522Ulcerative ColitisCytokinesTNF |
| spellingShingle | Marina Liso Giulio Verna Elisabetta Cavalcanti Stefania De Santis Raffaele Armentano Angela Tafaro Antonio Lippolis Pietro Campiglia Antonio Gasbarrini Mauro Mastronardi Theresa Torres Pizarro Fabio Cominelli Loris Riccardo Lopetuso Marcello Chieppa Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative ColitisSummary Cellular and Molecular Gastroenterology and Hepatology Ulcerative Colitis Cytokines TNF |
| title | Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative ColitisSummary |
| title_full | Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative ColitisSummary |
| title_fullStr | Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative ColitisSummary |
| title_full_unstemmed | Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative ColitisSummary |
| title_short | Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative ColitisSummary |
| title_sort | interleukin 1β blockade reduces intestinal inflammation in a murine model of tumor necrosis factor independent ulcerative colitissummary |
| topic | Ulcerative Colitis Cytokines TNF |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X22000522 |
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