PMID- 38141180
OWN - NLM
STAT- Publisher
LR  - 20240305
IS  - 1536-4844 (Electronic)
IS  - 1078-0998 (Linking)
DP  - 2023 Dec 23
TI  - Monoclonal Antibody Against Mature Interleukin-18 Ameliorates Colitis in Mice and 
      Improves Epithelial Barrier Function.
LID - izad292 [pii]
LID - 10.1093/ibd/izad292 [doi]
AB  - BACKGROUND: Antitumor necrosis factor (TNF)-alpha antibodies have improved the 
      outcome of inflammatory bowel disease (IBD); but half of patients remain 
      unresponsive to treatment. Interleukin-18 (IL-18) gene polymorphism is associated 
      with resistance to anti-TNF-alpha antibodies, but therapies targeting IL-18 have not 
      been clinically applied. Only the mature protein is biologically active, and we 
      aimed to investigate whether specific inhibition of mature IL-18 using a 
      monoclonal antibody (mAb) against a neoepitope of caspase-cleaved mature IL-18 
      could be an innovative treatment for IBD. METHODS: The expression of precursor 
      and mature IL-18 in patients with UC was examined. Colitis was induced in C57/BL6 
      mice by administering dextran sulfate sodium (DSS), followed by injection with 
      anti-IL-18 neoepitope mAb. Colon tissues were collected and subjected to 
      histological analysis, immunohistochemistry, immunoblotting, and quantitative 
      polymerase chain reaction. Colon epithelial permeability and microbiota 
      composition were analyzed. RESULTS: Mature IL-18 expression was elevated in colon 
      tissues of patients with active ulcerative colitis. Administration of anti-IL-18 
      neoepitope mAb ameliorated acute and chronic DSS-induced colitis; reduced 
      interferon-gamma, TNF-alpha, and chemokine (CXC motif) ligand-2 production and epithelial 
      cell permeability; promoted goblet cell function; and altered the intestinal 
      microbiome composition. The suppressive effect of anti-IL-18 neoepitope mAb was 
      superior to that of anti-whole IL-18 mAb. Furthermore, combination therapy with 
      anti-TNF-alpha Ab suppressed acute and chronic colitis additively by suppressing 
      cytokine expressions and reducing cell permeability by upregulating claudin1 and 
      occludin expression. CONCLUSIONS: Anti-IL-18 neoepitope mAb ameliorates acute and 
      chronic colitis, suggesting that this mAb will be an innovative therapeutic 
      option for IBD.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & 
      Colitis Foundation. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Ikegami, Shuji
AU  - Ikegami S
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Maeda, Keiko
AU  - Maeda K
AUID- ORCID: 0000-0001-6477-1865
AD  - Department of Endoscopy, Nagoya University Graduate School of Medicine, 65 
      Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Urano, Takeshi
AU  - Urano T
AD  - Department of Biochemistry, Shimane University School of Medicine, Izumo 
      693-8501, Japan.
AD  - mAbProtein Co. Ltd., Izumo 693-8501, Japan.
FAU - Mu, Jingxi
AU  - Mu J
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Nakamura, Masanao
AU  - Nakamura M
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Yamamura, Takeshi
AU  - Yamamura T
AUID- ORCID: 0000-0003-4994-016X
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Sawada, Tsunaki
AU  - Sawada T
AD  - Department of Endoscopy, Nagoya University Graduate School of Medicine, 65 
      Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Ishikawa, Eri
AU  - Ishikawa E
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Yamamoto, Kenta
AU  - Yamamoto K
AD  - Department of Endoscopy, Nagoya University Graduate School of Medicine, 65 
      Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Muto, Hisanori
AU  - Muto H
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Oishi, Akina
AU  - Oishi A
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Iida, Tadashi
AU  - Iida T
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Mizutani, Yasuyuki
AU  - Mizutani Y
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Ishikawa, Takuya
AU  - Ishikawa T
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Kakushima, Naomi
AU  - Kakushima N
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Furukawa, Kazuhiro
AU  - Furukawa K
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Ohno, Eizaburo
AU  - Ohno E
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Honda, Takashi
AU  - Honda T
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Ishigami, Masatoshi
AU  - Ishigami M
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Kawashima, Hiroki
AU  - Kawashima H
AD  - Department of Gastroenterology and Hepatology, Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
LA  - eng
GR  - JP19K20667/Japan Society for the Promotion of Science/
GR  - A138/Japan Agency for Medical Research and Development, AMED/
PT  - Journal Article
DEP - 20231223
PL  - England
TA  - Inflamm Bowel Dis
JT  - Inflammatory bowel diseases
JID - 9508162
SB  - IM
CIN - Inflamm Bowel Dis. 2024 Apr 3;30(4):693-694. PMID: 38442894
CIN - Inflamm Bowel Dis. 2024 Apr 3;30(4):695-696. PMID: 38442897
OAB - We investigate a novel monoclonal antibody that specifically recognizes a 
      neoepitope of caspase-cleaved IL-18 and alleviates dextran sulfate sodium-induced 
      colitis by suppressing the secretion of inflammatory cytokines, improving 
      intestinal epithelial permeability, promoting goblet cell function, and 
      regulating intestinal microbiota.
OABL- eng
OTO - NOTNLM
OT  - IL-18
OT  - cytokine
OT  - inflammatory bowel disease
OT  - ulcerative colitis
EDAT- 2023/12/23 22:53
MHDA- 2023/12/23 22:53
CRDT- 2023/12/23 15:35
PHST- 2022/05/20 00:00 [received]
PHST- 2023/12/23 22:53 [medline]
PHST- 2023/12/23 22:53 [pubmed]
PHST- 2023/12/23 15:35 [entrez]
AID - 7492619 [pii]
AID - 10.1093/ibd/izad292 [doi]
PST - aheadofprint
SO  - Inflamm Bowel Dis. 2023 Dec 23:izad292. doi: 10.1093/ibd/izad292.