Digestive Diseases and Sciences

, Volume 56, Issue 12, pp 3525–3533 | Cite as

Th1 Responses Are More Susceptible to Infliximab-Mediated Immunosuppression Than Th17 Responses

  • Kenji Kanayama
  • Kazuhiko Nakamura
  • Haruei Ogino
  • Yorinobu Sumida
  • Eikichi Ihara
  • Hirotada Akiho
  • Ryoichi Takayanagi
Original Article



Treatment with infliximab, a chimeric anti-tumor necrosis factor (TNF)-α antibody, is highly efficient in patients with inflammatory bowel disease (IBD). It neutralizes soluble TNF-α and induces the apoptosis of transmembrane TNF-α-positive macrophages and T cells in the gut. Recently, T helper (Th)17, as well as Th1, responses have been implicated in the pathogenesis of IBD.


To clarify the effects of infliximab on Th1 and Th17 responses in vitro.


Naive CD4+ T cells isolated from the peripheral blood of healthy volunteers were stimulated under Th1- or Th17-inducing conditions in the presence of 10 μg/ml of infliximab or control immunoglobulin (Ig)G1. The concentrations of interferon (IFN)-γ, interleukin (IL)-17, and TNF-α in the culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). Th1 and Th17 cells were immunostained with infliximab or control IgG1 and transmembrane TNF-α-positive cells were analyzed by flow cytometry. Annexin V staining and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) assays were conducted in order to analyze the percentage of apoptotic cells.


Both Th1 and Th17 cells expressed soluble and transmembrane TNF-α abundantly. Although infliximab suppressed IFN-γ secretion by Th1 cells and IL-17 secretion by Th17 cells, the level of the former was more profound than the latter. Infliximab increased annexin V- and TUNEL-positive apoptotic cells under Th1-inducing conditions, but not under Th17-inducing conditions.


Infliximab suppressed Th1 and Th17 differentiation in vitro; however, IFN-γ production by Th1 cells was more profoundly suppressed than IL-17 secretion by Th17 cells. Th1 responses were more susceptible to infliximab-mediated apoptosis than Th17 responses. Our results clarify a new mechanism of action of infliximab.


Infliximab Tumor necrosis factor-α T helper 1 T helper 17 Apoptosis 


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kenji Kanayama
    • 1
  • Kazuhiko Nakamura
    • 1
  • Haruei Ogino
    • 1
  • Yorinobu Sumida
    • 1
  • Eikichi Ihara
    • 1
  • Hirotada Akiho
    • 1
  • Ryoichi Takayanagi
    • 1
  1. 1.Department of Medicine and Bioregulatory Science, Graduate School of Medical SciencesKyushu UniversityHigashi-kuJapan

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