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31.08.2021 | Original Article

Antibacterial and Immunosuppressive Effects of OPS-2071, a Candidate Therapy for Inflammatory Bowel Disease

verfasst von: Masayoshi Sato, Kazuyuki Fujii, Hiroko Takagi, Isao Shibuya, Daisuke Oka, Naomitsu Yamaya, Hiraku Hagita, Makoto Matsumoto, Katsuya Inagaki

Erschienen in: Digestive Diseases and Sciences | Ausgabe 8/2022

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Abstract

Background

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Although many types of drug are used, clinical outcomes are still unsatisfactory. Previous studies have suggested that intestinal bacteria are involved in the pathogenesis of IBD. Accordingly, in an IBD model we evaluated the therapeutic effects of OPS-2071, a low-absorption quinolone antibacterial agent indicated for intestinal infection, and investigated its mechanism of action.

Methods

The therapeutic effects of OPS-2071 and comparison therapies were evaluated using naive CD4 + T cell-transfer IBD model mice. In vitro inhibition of LPS-induced TNF-α production and inhibitory effects on T cell responses stimulated using anti-CD3/CD28 antibody-loaded beads were evaluated using mouse splenocytes and human peripheral blood mononuclear cells. In addition, in vitro activities against bacteria implicated in IBD pathogenesis were tested.

Results

OPS-2071 dose-dependently decreased both colonic weight/length ratio and the colitis histological score as compared with the vehicle group. The therapeutic effect of OPS-2071 was equivalent to that of anti-IL-12/23 (p40) antibody. In vitro, OPS-2071 suppressed TNF-α production induced by LPS stimulation and T cell responses in a dose-dependent manner. At high concentrations, these effects were comparable to those of existing immunosuppressive agents, such as prednisolone, in both mouse and human cells. OPS-2071 also showed antibacterial activity against IBD-related bacteria.

Conclusions

Our results suggest that OPS-2071 had both immunosuppressive and antibacterial effects. This dual effect makes OPS-2071 a unique and promising candidate for IBD.

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Titel: Antibacterial and Immunosuppressive Effects of OPS-2071, a Candidate Therapy for Inflammatory Bowel Disease
verfasst von: Masayoshi Sato
Kazuyuki Fujii
Hiroko Takagi
Isao Shibuya
Daisuke Oka
Naomitsu Yamaya
Hiraku Hagita
Makoto Matsumoto
Katsuya Inagaki
Publikationsdatum: 31.08.2021
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 8/2022
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-021-07237-2

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Antibacterial and Immunosuppressive Effects of OPS-2071, a Candidate Therapy for Inflammatory Bowel Disease

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Background

Methods

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Conclusions

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