Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis
Copyright © 2023 Lindemann, Roth, Koop, Neufert, Zundler, Atreya, Neurath and Leppkes..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Frontiers in medicine - 10(2023) vom: 04., Seite 1177450 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lindemann, Aylin [VerfasserIn] |
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| Links: |
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| Themen: |
Calcineurin inhibitors |
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| Anmerkungen: |
Date Revised 01.07.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fmed.2023.1177450 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM35860351X |
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| 245 | 1 | 0 | |a Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis |
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| 500 | |a Date Revised 01.07.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2023 Lindemann, Roth, Koop, Neufert, Zundler, Atreya, Neurath and Leppkes. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a IBD | |
| 650 | 4 | |a calcineurin inhibitors | |
| 650 | 4 | |a steroid refractory colitis | |
| 650 | 4 | |a ulcerative colitis | |
| 650 | 4 | |a voclosporin | |
| 700 | 1 | |a Roth, Dominik |e verfasserin |4 aut | |
| 700 | 1 | |a Koop, Kristina |e verfasserin |4 aut | |
| 700 | 1 | |a Neufert, Clemens |e verfasserin |4 aut | |
| 700 | 1 | |a Zundler, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Atreya, Raja |e verfasserin |4 aut | |
| 700 | 1 | |a Neurath, Markus F |e verfasserin |4 aut | |
| 700 | 1 | |a Leppkes, Moritz |e verfasserin |4 aut | |
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