Vol.20 No.2

Original Article

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

Authors

Atsushi Ogata1 , Masahide Mori2 , Shoji Hashimoto3 , Yukihiro Yano2 , Takeya Fujikawa2 , Mari Kawai1 , Yusuke Kuwahara1 , Toru Hirano1 , Junsuke Arimitsu1 , Keisuke Hagihara1 , Yoshihito Shima1 , Masashi Narazaki1, Souichirou Yokota2, Tadamitsu Kishimoto4, Ichiro Kawase1, Toshio Tanaka1

  • Department of Respiratory Medicine, Allergy and Rheumatic Disease, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan
  • Department of Respiratory Medicine, National Hospital Organization Toneyama National Hospital, Osaka, Japan
  • Division of Infection Control and Prevention, Osaka University Hospital, Osaka, Japan
  • Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, Osaka, Japan
Received:

1 September 2009

Accepted:

1 October 2009

Published online:

7 November 2009

Full Text

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Abstract

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.

Key words

Interferon gamma - Interleukin-6 - Tocilizumab - Tuberculosis - Tumor necrosis factor