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

By Masaji Okada, Yoko Kita, Noriko Kanamaru, Satomi Hashimoto, Yasushi Uchiyama, Masahiko Mihara, Yoshikazu Inoue, Yoshiyuki Ohsugi, Tadamitsu Kishimoto and Mitsunori Sakatani

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

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3095415
Provided by: PubMed Central

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