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Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis

BACKGROUND AND AIMS: Acute severe steroid-refractory ulcerative colitis remains a medically challenging condition with frequent need of surgery. It can be treated with the calcineurin inhibitor cyclosporine A with the need for therapeutic drug monitoring and significant toxicity. Recently, a novel c...

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Autores principales: Lindemann, Aylin, Roth, Dominik, Koop, Kristina, Neufert, Clemens, Zundler, Sebastian, Atreya, Raja, Neurath, Markus F., Leppkes, Moritz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289195/
https://www.ncbi.nlm.nih.gov/pubmed/37358998
http://dx.doi.org/10.3389/fmed.2023.1177450
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author Lindemann, Aylin
Roth, Dominik
Koop, Kristina
Neufert, Clemens
Zundler, Sebastian
Atreya, Raja
Neurath, Markus F.
Leppkes, Moritz
author_facet Lindemann, Aylin
Roth, Dominik
Koop, Kristina
Neufert, Clemens
Zundler, Sebastian
Atreya, Raja
Neurath, Markus F.
Leppkes, Moritz
author_sort Lindemann, Aylin
collection PubMed
description BACKGROUND AND AIMS: Acute severe steroid-refractory ulcerative colitis remains a medically challenging condition with frequent need of surgery. It can be treated with the calcineurin inhibitor cyclosporine A with the need for therapeutic drug monitoring and significant toxicity. Recently, a novel calcineurin inhibitor, voclosporin, has been approved for the treatment of lupus nephritis with no need for therapeutic drug monitoring and an improved long-term safety profile. However, the therapeutic effect of voclosporin in acute severe steroid-refractory ulcerative colitis is still uncertain. We aimed to assess the therapeutic potential of voclosporin to ameliorate inflammation in an experimental model of colitis. METHODS: We used the dextran sodium sulfate-induced model of colitis in C57BL/6 J wildtype mice treated with either cyclosporine A, voclosporin or solvent control. We employed endoscopy, histochemistry, immunofluorescence, bead-based multiplex immunoassays and flow cytometry to study the therapeutic effect of calcineurin inhibitors in a preventive setting. RESULTS: Acute colitis was induced by dextran sodium sulfate characterized by weight loss, diarrhea, mucosal erosions and rectal bleeding. Both cyclosporine A and voclosporin strongly ameliorated the course of disease and reduced colitis severity in a similar manner. CONCLUSION: Voclosporin was identified as biologically effective in a preclinical model of colitis and may be a potential therapeutic option in treating acute severe steroid-refractory ulcerative colitis.
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spelling pubmed-102891952023-06-24 Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis Lindemann, Aylin Roth, Dominik Koop, Kristina Neufert, Clemens Zundler, Sebastian Atreya, Raja Neurath, Markus F. Leppkes, Moritz Front Med (Lausanne) Medicine BACKGROUND AND AIMS: Acute severe steroid-refractory ulcerative colitis remains a medically challenging condition with frequent need of surgery. It can be treated with the calcineurin inhibitor cyclosporine A with the need for therapeutic drug monitoring and significant toxicity. Recently, a novel calcineurin inhibitor, voclosporin, has been approved for the treatment of lupus nephritis with no need for therapeutic drug monitoring and an improved long-term safety profile. However, the therapeutic effect of voclosporin in acute severe steroid-refractory ulcerative colitis is still uncertain. We aimed to assess the therapeutic potential of voclosporin to ameliorate inflammation in an experimental model of colitis. METHODS: We used the dextran sodium sulfate-induced model of colitis in C57BL/6 J wildtype mice treated with either cyclosporine A, voclosporin or solvent control. We employed endoscopy, histochemistry, immunofluorescence, bead-based multiplex immunoassays and flow cytometry to study the therapeutic effect of calcineurin inhibitors in a preventive setting. RESULTS: Acute colitis was induced by dextran sodium sulfate characterized by weight loss, diarrhea, mucosal erosions and rectal bleeding. Both cyclosporine A and voclosporin strongly ameliorated the course of disease and reduced colitis severity in a similar manner. CONCLUSION: Voclosporin was identified as biologically effective in a preclinical model of colitis and may be a potential therapeutic option in treating acute severe steroid-refractory ulcerative colitis. Frontiers Media S.A. 2023-06-09 /pmc/articles/PMC10289195/ /pubmed/37358998 http://dx.doi.org/10.3389/fmed.2023.1177450 Text en Copyright © 2023 Lindemann, Roth, Koop, Neufert, Zundler, Atreya, Neurath and Leppkes. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Lindemann, Aylin
Roth, Dominik
Koop, Kristina
Neufert, Clemens
Zundler, Sebastian
Atreya, Raja
Neurath, Markus F.
Leppkes, Moritz
Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis
title Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis
title_full Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis
title_fullStr Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis
title_full_unstemmed Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis
title_short Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis
title_sort protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289195/
https://www.ncbi.nlm.nih.gov/pubmed/37358998
http://dx.doi.org/10.3389/fmed.2023.1177450
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