title: Minimal influence of tocilizumab on IFN-gamma synthesis by tuberculosis antigens.
abstract: Interferon gamma (IFN-gamma) 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-gamma production. MTB antigen (ESAT-6 and CFP-10)-induced IFN-gamma-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-gamma production in a dose-dependent manner. In whole blood from TB patients, ESAT-6 stimulated significant production of IFN-gamma (1.30 +/- 1.95 IU/ml), and TCZ did not inhibit IFN-gamma production (1.56 +/- 1.88 IU/ml). IFN-gamma 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-gamma (1.46 +/- 1.60 IU/ml), and TCZ did not inhibit IFN-gamma production (1.51 +/- 1.77 IU/ml). IFN-gamma 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-gamma production. As IFN-gamma production is important in antimycobacterial host defenses, the minimal influence of TCZ on IFN-gamma-releasing assay suggests a low risk of latent TB infection reactivation during tocilizumab therapy.
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan. ogata@imed3.med.osaka-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogata
authors.forename: Masahide
authors.initials: M
authors.lastname: Mori
authors.forename: Shoji
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yano
authors.forename: Takeya
authors.initials: T
authors.lastname: Fujikawa
authors.forename: Mari
authors.initials: M
authors.lastname: Kawai
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kuwahara
authors.forename: Toru
authors.initials: T
authors.lastname: Hirano
authors.forename: Junsuke
authors.initials: J
authors.lastname: Arimitsu
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hagihara
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Shima
authors.forename: Masashi
authors.initials: M
authors.lastname: Narazaki
authors.forename: Souichirou
authors.initials: S
authors.lastname: Yokota
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007155:Immunologic Factors; D007371:Interferon-gamma; C502936:tocilizumab