Research Papers: Immunology:
Inhibition of autoimmune Th17 cell responses by pain killer ketamine
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Jeong-Eun Lee1,2,*, Jung-Man Lee3,*, Young-Jun Park1, Byung-Seok Kim1,2, Young-Tae Jeon4,5 and Yeonseok Chung1,2
1 Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, Republic of Korea
2 BK21 plus program, College of Pharmacy, Seoul National University, Seoul, Republic of Korea
3 Department of Anesthesiology and Pain Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea
4 Department of Anesthesiology and Pain Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea
5 Department of Anesthesiology and Pain Medicine, College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
* These authors have equally contributed to this work
Yeonseok Chung, email:
Young-Tae Jeon, email:
Keywords: ketamine, Th17 cell, STAT3, IL-21, autoimmunity, Immunology and Microbiology Section, Immune response, Immunity
Received: April 04, 2017 Accepted: May 23, 2017 Published: May 31, 2017
Ketamine is widely used in animals and humans as a systemic anesthetic. Although several immune-modulatory functions of ketamine have been reported, the effects of ketamine on the differentiation of Th17 cell are unknown. We found that ketamine significantly diminished the frequency of IL-17-producers among CD4+ T cells stimulated under Th17-skewing conditions. Mechanistic studies showed that ketamine had little effect on the production of Th17-inducing cytokines by dendritic cells and the proliferation of T cells in response to anti-CD3; however it significantly hampered IL-21 expression as well as STAT3 phosphorylation in T cells upon IL-6 stimulation. Moreover, MOG-reactive CD4+ T cells expanded in the presence of ketamine produced reduced amounts of Th17 cytokines, leading to diminished EAE severity when transferred into TCRβ-deficient mice in comparison to those treated with vehicle. These findings demonstrate that ketamine suppresses autoimmune Th17 cell responses by inhibiting the differentiation as well as the reactivation of Th17 cells.
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