Cargando…
Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative Colitis
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% o...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120241/ https://www.ncbi.nlm.nih.gov/pubmed/35314399 http://dx.doi.org/10.1016/j.jcmgh.2022.03.003 |
_version_ | 1784710894355218432 |
---|---|
author | Liso, Marina Verna, Giulio Cavalcanti, Elisabetta De Santis, Stefania Armentano, Raffaele Tafaro, Angela Lippolis, Antonio Campiglia, Pietro Gasbarrini, Antonio Mastronardi, Mauro Pizarro, Theresa Torres Cominelli, Fabio Lopetuso, Loris Riccardo Chieppa, Marcello |
author_facet | Liso, Marina Verna, Giulio Cavalcanti, Elisabetta De Santis, Stefania Armentano, Raffaele Tafaro, Angela Lippolis, Antonio Campiglia, Pietro Gasbarrini, Antonio Mastronardi, Mauro Pizarro, Theresa Torres Cominelli, Fabio Lopetuso, Loris Riccardo Chieppa, Marcello |
author_sort | Liso, Marina |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9120241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-91202412022-05-21 Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative Colitis Liso, Marina Verna, Giulio Cavalcanti, Elisabetta De Santis, Stefania Armentano, Raffaele Tafaro, Angela Lippolis, Antonio Campiglia, Pietro Gasbarrini, Antonio Mastronardi, Mauro Pizarro, Theresa Torres Cominelli, Fabio Lopetuso, Loris Riccardo Chieppa, Marcello Cell Mol Gastroenterol Hepatol Original Research 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. Elsevier 2022-03-18 /pmc/articles/PMC9120241/ /pubmed/35314399 http://dx.doi.org/10.1016/j.jcmgh.2022.03.003 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Liso, Marina Verna, Giulio Cavalcanti, Elisabetta De Santis, Stefania Armentano, Raffaele Tafaro, Angela Lippolis, Antonio Campiglia, Pietro Gasbarrini, Antonio Mastronardi, Mauro Pizarro, Theresa Torres Cominelli, Fabio Lopetuso, Loris Riccardo Chieppa, Marcello Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative Colitis |
title | Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative Colitis |
title_full | Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative Colitis |
title_fullStr | Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative Colitis |
title_full_unstemmed | Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative Colitis |
title_short | Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative Colitis |
title_sort | interleukin 1β blockade reduces intestinal inflammation in a murine model of tumor necrosis factor–independent ulcerative colitis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120241/ https://www.ncbi.nlm.nih.gov/pubmed/35314399 http://dx.doi.org/10.1016/j.jcmgh.2022.03.003 |
work_keys_str_mv | AT lisomarina interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT vernagiulio interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT cavalcantielisabetta interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT desantisstefania interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT armentanoraffaele interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT tafaroangela interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT lippolisantonio interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT campigliapietro interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT gasbarriniantonio interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT mastronardimauro interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT pizarrotheresatorres interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT cominellifabio interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT lopetusolorisriccardo interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis AT chieppamarcello interleukin1bblockadereducesintestinalinflammationinamurinemodeloftumornecrosisfactorindependentulcerativecolitis |