Comparative Analysis of the Effects of Anti-IL-6 Receptor mAb and Anti-TNF mAb Treatment on CD4(+) T-cell Responses in Murine Colitis
SCIE
SCOPUS
- Title
- Comparative Analysis of the Effects of Anti-IL-6 Receptor mAb and Anti-TNF mAb Treatment on CD4(+) T-cell Responses in Murine Colitis
- Authors
- Terabe, F; Fujimoto, M; Serada, S; Shinzaki, S; Iijima, H; Tsujii, M; Hayashi, N; Nomura, S; Kawahata, H; Jang, MH; Miyasaka, M; Mihara, M; Ohsugi, Y; Kishimoto, T; Naka, T
- Date Issued
- 2011-02
- Publisher
- WILEY-BLACKWELL
- Abstract
- Background: The efficacy of anti-tumor necrosis factor monoclonal antibody (anti-TNF mAb) for Crohn's disease (CD) is well established, and anti-interleukin-6 receptor (anti-IL-6R) mAb has also been reported to be effective in CD. It is, however, unclear if the efficacy and mechanisms of both agents are different in CD therapy. Methods: Using an adoptive transfer colitis model, we compared the efficacy of anti-IL-6R mAb, anti-TNF mAb, and TNF receptor-Fc fusion protein (TNFR-Fc), and their modes of action on CD4(+) T cells. We also investigated the role of Th1 and Th17 cells in colitis using the same model. Results: The histological scores for the anti-IL-6R mAb and anti-TNF mAb groups but not for TNFR-Fc group were much lower than that for the control group, and the score was the lowest for the anti-IL-6R mAb group. The frequency of proliferating CD4(+) T cells was reduced in anti-IL-6R mAb and anti-TNF mAb groups, but not in the TNFR-Fc group, whereas the frequency of apoptotic CD4(+) T cells was similar in all groups. Anti-IL-6R mAb suppressed the induction of Th17 cells and increased the frequency of lamina propria regulatory T cells, whereas anti-TNF mAb exerted no influence on CD4(+) T-cell differentiation. A deficiency in interferon-gamma and/or IL-17 in CD4(+) T cells reduced the severity of colitis. Conclusions: Our findings suggest that suppression of the proliferation of pathogenic CD4(+) T cells is the major mode of action of biological agents for colitis therapy. Anti-IL-6R mAb might have benefits in CD patients with Th17 dominance and impaired Treg frequency.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/92465
- DOI
- 10.1002/IBD.21384
- ISSN
- 1078-0998
- Article Type
- Article
- Citation
- INFLAMMATORY BOWEL DISEASES, vol. 17, no. 2, page. 491 - 502, 2011-02
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