Interleukin-21 and tumor necrosis factor-α are critical for the development of autoimmune gastritis in mice.

Abstract

BACKGROUND AND AIM:

Autoimmune gastritis (AIG), an organ-specific autoimmune disease, is accompanied by achlorhydria, pernicious anemia, gastric carcinoid tumors, and gastric cancer. Patients with AIG initially respond to corticosteroids but have a great potential to relapse after treatment is withdrawn. This study examines the roles of cytokines in order to identify potential therapeutic options for AIG patients.

METHODS:

Using a mouse model of AIG, we monitored disease progression and administered antibodies in vivo to block cytokines.

RESULTS:

We developed a mouse model of AIG with early onset and rapid progression in which neonatal thymectomy (NTx) was performed on programmed cell death 1-deficient (PD-1(-/-) ) mice on the BALB/c background. Using NTx-PD-1(-/-) mice, we found that in AIG lesions, interferon-γ, and tumor necrosis factor (TNF)-α together with interleukin-21 (IL-21) were highly expressed in the inflamed gastric mucosa. In addition, as with the injection of dexamethasone, in vivo administration of either anti-TNF-α or anti-IL-21 suppressed the development of AIG in NTx-PD-1(-/-) mice.

CONCLUSIONS:

These data reveal the essential role of IL-21 in the development of AIG and suggest that in addition to corticosteroids, anti-TNF-α as well as anti-IL-21 have the potential to induce the remission of AIG, offering additional therapeutic options for AIG patients.

• Authors: Hisayo Nishiura, Satoru Iwamoto, Masahiro Kido, Nobuhiro Aoki, Ryutaro Maruoka, Aki Ikeda, Tsutomu Chiba, Norihiko Watanabe
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 28 Issue 6 Pg. 982-91 (Jun 2013) ISSN: 1440-1746 [Electronic] Australia
• PMID: 23425147 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Chemical References

• Interleukins
• Tumor Necrosis Factor-alpha
• interleukin-21

Topics

• Animals
• Autoimmune Diseases (immunology)
• Gastritis (immunology)
• Interleukins (immunology)
• Mice
• Mice, Inbred BALB C
• Tumor Necrosis Factor-alpha (immunology)