Anti-IL-6 Receptor Antibody Causes Less Promotion of Tuberculosis Infection than Anti-TNF-𝛼 Antibody in Mice
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...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2011/404929 |
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| author | Masaji Okada Yoko Kita Noriko Kanamaru Satomi Hashimoto Yasushi Uchiyama Masahiko Mihara Yoshikazu Inoue Yoshiyuki Ohsugi Tadamitsu Kishimoto Mitsunori Sakatani |
| author_facet | Masaji Okada Yoko Kita Noriko Kanamaru Satomi Hashimoto Yasushi Uchiyama Masahiko Mihara Yoshikazu Inoue Yoshiyuki Ohsugi Tadamitsu Kishimoto Mitsunori Sakatani |
| author_sort | Masaji Okada |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-630960e866234d10a47fe6308fe37e18 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-630960e866234d10a47fe6308fe37e182025-02-03T01:23:04ZengWileyClinical and Developmental Immunology1740-25221740-25302011-01-01201110.1155/2011/404929404929Anti-IL-6 Receptor Antibody Causes Less Promotion of Tuberculosis Infection than Anti-TNF-𝛼 Antibody in MiceMasaji Okada0Yoko Kita1Noriko Kanamaru2Satomi Hashimoto3Yasushi Uchiyama4Masahiko Mihara5Yoshikazu Inoue6Yoshiyuki Ohsugi7Tadamitsu Kishimoto8Mitsunori Sakatani9Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka 591-8555, JapanClinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka 591-8555, JapanClinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka 591-8555, JapanClinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka 591-8555, JapanChugai Pharmaceutical Co., Ltd., Product Research Department, Shizuoka 412-8513, JapanChugai Pharmaceutical Co., Ltd., Product Research Department, Shizuoka 412-8513, JapanClinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka 591-8555, JapanChugai Pharmaceutical Co., Ltd., Product Research Department, Shizuoka 412-8513, JapanLaboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, JapanClinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka 591-8555, JapanObjective. 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.http://dx.doi.org/10.1155/2011/404929 |
| spellingShingle | Masaji Okada Yoko Kita Noriko Kanamaru Satomi Hashimoto Yasushi Uchiyama Masahiko Mihara Yoshikazu Inoue Yoshiyuki Ohsugi Tadamitsu Kishimoto Mitsunori Sakatani Anti-IL-6 Receptor Antibody Causes Less Promotion of Tuberculosis Infection than Anti-TNF-𝛼 Antibody in Mice Clinical and Developmental Immunology |
| title | Anti-IL-6 Receptor Antibody Causes Less Promotion of Tuberculosis Infection than Anti-TNF-𝛼 Antibody in Mice |
| title_full | Anti-IL-6 Receptor Antibody Causes Less Promotion of Tuberculosis Infection than Anti-TNF-𝛼 Antibody in Mice |
| title_fullStr | Anti-IL-6 Receptor Antibody Causes Less Promotion of Tuberculosis Infection than Anti-TNF-𝛼 Antibody in Mice |
| title_full_unstemmed | Anti-IL-6 Receptor Antibody Causes Less Promotion of Tuberculosis Infection than Anti-TNF-𝛼 Antibody in Mice |
| title_short | Anti-IL-6 Receptor Antibody Causes Less Promotion of Tuberculosis Infection than Anti-TNF-𝛼 Antibody in Mice |
| title_sort | anti il 6 receptor antibody causes less promotion of tuberculosis infection than anti tnf 𝛼 antibody in mice |
| url | http://dx.doi.org/10.1155/2011/404929 |
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