Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-gamma and TNF-alpha production

Details

Serval ID
serval:BIB_7D692CC172C8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-gamma and TNF-alpha production
Journal
American Journal of Physiology-Regulatory Integrative and Comparative Physiology
Author(s)
Lehr HA, Siegmund B, Fantuzzi G, Rider F, Gamboni-Robertson F, Hartmann G, Dinarello CA, Endres S, Eigler A
ISSN
0363-6119
Publication state
Published
Issued date
2001
Peer-reviewed
Oui
Volume
281
Number
4
Pages
R1264-R1273
Language
english
Abstract
Interleukin (IL)-18, initially described as interferon (IFN)-gamma -inducing factor, is expressed in the inflamed mucosa of patients with Crohn's disease. To investigate the role of IL-18 in intestinal inflammation, the effect of neutralizing antimurine IL-18 antiserum in dextran sulfate sodium (DSS)-induced colitis in BALB/c and C57BL/6 mice was examined. During a dose response of DSS, levels of colonic IL-18 increased parallel with clinical worsening. With the use of confocal laser microscopy, the increased IL-18 was localized to the intestinal epithelial layer. Anti-IL-18 treatment resulted in a dose-dependent reduction of the severity of colitis in both BALB/c and C57BL/6 mice. Colon shortening following DSS-induced colitis was partially prevented in the treatment groups. In the colon tissue homogenates, IFN-gamma concentrations were lower in the anti-IL-18-treated DSS-fed mice compared with untreated DSS-fed mice. This suppressive effect of anti-IL-18 administered in vivo was also observed on spontaneous tumor necrosis factor-alpha, IL-18, and IFN-gamma production from ex vivo colon organ cultures. The stimulation of lamina propria mononuclear cells by IL-18 and IL-12 resulted in a synergistic increase in IFN-gamma synthesis. These findings suggest that IL-18 is a pivotal mediator in experimental colitis.
Keywords
inflammation, cytokines, antibodies, in vivo animal models, DEXTRAN SULFATE SODIUM, INFLAMMATORY BOWEL-DISEASE, NECROSIS-FACTOR-ALPHA, INTERFERON-GAMMA, CROHNS-DISEASE, PROINFLAMMATORY CYTOKINE, ULCERATIVE-COLITIS, T-CELLS, IMMUNODEFICIENT MICE, MONOCLONAL-ANTIBODY
Web of science
Create date
15/12/2011 21:06
Last modification date
20/08/2019 14:38
Usage data