caa a22 4500 445794828 CHVBK 20180317145121.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10620-011-1780-1 doi (NATIONALLICENCE)springer-10.1007/s10620-011-1780-1 Th1 Responses Are More Susceptible to Infliximab-Mediated Immunosuppression Than Th17 Responses [Elektronische Daten] [Kenji Kanayama, Kazuhiko Nakamura, Haruei Ogino, Yorinobu Sumida, Eikichi Ihara, Hirotada Akiho, Ryoichi Takayanagi] Background: 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. Aims: To clarify the effects of infliximab on Th1 and Th17 responses in vitro. Methods: Naive CD4+ T cells isolated from the peripheral blood of healthy volunteers were stimulated under Th1- or Th17-inducing conditions in the presence of 10μg/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. Results: 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. Conclusions: 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. Springer Science+Business Media, LLC, 2011 Infliximab nationallicence Tumor necrosis factor-α nationallicence T helper 1 nationallicence T helper 17 nationallicence Apoptosis nationallicence Kanayama Kenji Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Nakamura Kazuhiko Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Ogino Haruei Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Sumida Yorinobu Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Ihara Eikichi Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Akiho Hirotada Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Takayanagi Ryoichi Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/12(2011-12-01), 3525-3533 0163-2116 56:12<3525 2011 56 10620 https://doi.org/10.1007/s10620-011-1780-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-011-1780-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kanayama Kenji Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 700 1- Nakamura Kazuhiko Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 700 1- Ogino Haruei Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 700 1- Sumida Yorinobu Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 700 1- Ihara Eikichi Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 700 1- Akiho Hirotada Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 700 1- Takayanagi Ryoichi Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Higashi-ku, Fukuoka, Japan aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/12(2011-12-01), 3525-3533 0163-2116 56:12<3525 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer