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

作者：Okada Masaji^*; Kita Yoko; Kanamaru Noriko; Hashimoto Satomi; Uchiyama Yasushi; Mihara Masahiko; Inoue Yoshikazu; Ohsugi Yoshiyuki; Kishimoto Tadamitsu; Sakatani Andmitsunori

来源：Clinical and Developmental Immunology, 2011, 404929.

DOI：10.1155/2011/404929

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-alpha 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-alpha 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-alpha Ab-treated mice exhibited increased TB CFU and greater progression of histopathological findings in organs than control mice. Spleen cells from anti-TNF-alpha Ab-treated mice had decreased antigen-specific response in IFN-gamma 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-alpha blockade.

• 出版日期2011