Minimal influence of tocilizumab on IFN-γ synthesis by tuberculosis antigens

• Published in: Modern rheumatology 2010-04, Vol.20 (2), p.130-133
• Main Authors: Ogata, Atsushi, Mori, Masahide, Hashimoto, Shoji, Yano, Yukihiro, Fujikawa, Takeya, Kawai, Mari, Kuwahara, Yusuke, Hirano, Toru, Arimitsu, Junsuke, Hagihara, Keisuke, Shima, Yoshihito, Narazaki, Masashi, Yokota, Souichirou, Kishimoto, Tadamitsu, Kawase, Ichiro, Tanaka, Toshio
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Antigens, Bacterial; Bacterial Proteins; Humans; Immunologic Factors - pharmacology; Interferon-gamma - metabolism; Medicine; Medicine & Public Health; Original Article; Orthopedics; Rheumatology; Tuberculosis - immunology
• ISSN: 1439-7595; 1439-7609
• DOI: 10.1007/s10165-009-0243-4

Interferon gamma (IFN-γ) production is a critical step of antituberculosis (anti-TB) immune response. The purpose of this study was to determine the influences of biologics, including the interleukin (IL)-6 receptor-inhibitor tocilizumab (TCZ), and tumor necrosis factor (TNF) antagonists infliximab (INF) and etanercept (ETA), on Mycobacterium tuberculosis (MTB) antigen-induced IFN-γ production. MTB antigen (ESAT-6 and CFP-10)-induced IFN-γ-releasing assay was performed with or without addition of biologics (TCZ, ETA, and INF) using whole blood from patients with active TB. ETA and INF inhibited IFN-γ production in a dose-dependent manner. In whole blood from TB patients, ESAT-6 stimulated significant production of IFN-γ (1.30 ± 1.95 IU/ml), and TCZ did not inhibit IFN-γ production (1.56 ± 1.88 IU/ml). IFN-γ production by ESAT-6 was inhibited by ETA and INF (0.98 ± 1.74, 0.75 ± 1.66 IU/ml, respectively). CFP-10 stimulated significant production of IFN-γ (1.46 ± 1.60 IU/ml), and TCZ did not inhibit IFN-γ production (1.51 ± 1.77 IU/ml). IFN-γ production by CFP-10 was inhibited by ETA and INF (0.91 ± 0.99, 0.72 ± 0.88 IU/ml, respectively). TCD did not inhibit MTB antigen-induced IFN-γ production. As IFN-γ production is important in antimycobacterial host defenses, the minimal influence of TCZ on IFN-γ-releasing assay suggests a low risk of latent TB infection reactivation during tocilizumab therapy.