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Clinical and Developmental Immunology
Volume 2011, Article ID 404929, 9 pages
http://dx.doi.org/10.1155/2011/404929
Research Article

Anti-IL-6 Receptor Antibody Causes Less Promotion of Tuberculosis Infection than Anti-TNF- 𝛼 Antibody in Mice

1Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka 591-8555, Japan
2Chugai Pharmaceutical Co., Ltd., Product Research Department, Shizuoka 412-8513, Japan
3Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan

Received 15 October 2010; Revised 24 December 2010; Accepted 28 January 2011

Academic Editor: Hiroshi Nakajima

Copyright © 2011 Masaji Okada et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective. Our aim was to investigate the effects of IL-6 blockade on the progression of Mycobacterium tuberculosis (TB) and compare them with those of TNF-α blockade in mice. Methods. Mice were intravenously infected with TB and injected with antibodies. Survival was monitored and histological and immunological studies were carried out. Results. All anti-IL-6R Ab-treated mice and 8 of 10 control mice survived until sacrificed 224 days after TB challenge, whereas anti-TNF-α Ab-treated mice all died between 120 and 181 days. Anti-IL-6R Ab-treated mice exhibited no significant differences in TB CFU in organs, including the lungs, and no deterioration in histopathology compared to control mice at 4 weeks. In contrast, anti-TNF-α Ab-treated mice exhibited increased TB CFU and greater progression of histopathological findings in organs than control mice. Spleen cells from anti-TNF-α Ab-treated mice had decreased antigen-specific response in IFN-γ release and proliferation assays. The results in anti-IL-6R Ab-treated mice suggest that spleen cell responses were decreased to a lesser degree. Similar results were obtained in IL-6 knockout (KO) mice, compared with TNF receptor 1 (TNFR1) KO and TNFR1/IL-6 double KO (DKO) mice. Conclusion. IL-6R blockade promotes the progression of TB infection in mice far less than TNF-α blockade.