Quetiapine, an atypical antipsychotic, is protective against autoimmune-mediated demyelination by inhibiting effector T cell proliferation

Feng Mei; Sheng Guo; Yangtao He; Linyun Wang; Hongkai Wang; Jianqin Niu; Jiming Kong; Xinmin Li; Yuzhang Wu; Lan Xiao

doi:10.1371/journal.pone.0042746

Quetiapine, an atypical antipsychotic, is protective against autoimmune-mediated demyelination by inhibiting effector T cell proliferation

PLoS One. 2012;7(8):e42746. doi: 10.1371/journal.pone.0042746. Epub 2012 Aug 13.

Authors

Feng Mei¹, Sheng Guo, Yangtao He, Linyun Wang, Hongkai Wang, Jianqin Niu, Jiming Kong, Xinmin Li, Yuzhang Wu, Lan Xiao

Affiliation

¹ Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, China.

Abstract

Quetiapine (Que), a commonly used atypical antipsychotic drug (APD), can prevent myelin from breakdown without immune attack. Multiple sclerosis (MS), an autoimmune reactive inflammation demyelinating disease, is triggered by activated myelin-specific T lymphocytes (T cells). In this study, we investigated the potential efficacy of Que as an immune-modulating therapeutic agent for experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. Que treatment was initiated on the onset of MOG(35-55) peptide induced EAE mice and the efficacy of Que on modulating the immune response was determined by Flow Cytometry through analyzing CD4(+)/CD8(+) populations and the proliferation of effector T cells (CD4(+)CD25(-)) in peripheral immune organs. Our results show that Que dramatically attenuates the severity of EAE symptoms. Que treatment decreases the extent of CD4(+)/CD8(+) T cell infiltration into the spinal cord and suppresses local glial activation, thereby diminishing the loss of mature oligodendrocytes and myelin breakdown in the spinal cord of EAE mice. Our results further demonstrate that Que treatment decreases the CD4(+)/CD8(+) T cell populations in lymph nodes and spleens of EAE mice and inhibits either MOG(35-55) or anti-CD3 induced proliferation as well as IL-2 production of effector T cells (CD4(+)CD25(-)) isolated from EAE mice spleen. Together, these findings suggest that Que displays an immune-modulating role during the course of EAE, and thus may be a promising candidate for treatment of MS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antipsychotic Agents / pharmacology*
Astrocytes / drug effects
Astrocytes / pathology
CD4-Positive T-Lymphocytes / drug effects*
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / pathology*
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / pathology
Cell Proliferation / drug effects
Dibenzothiazepines / pharmacology*
Encephalomyelitis, Autoimmune, Experimental / chemically induced
Encephalomyelitis, Autoimmune, Experimental / immunology*
Encephalomyelitis, Autoimmune, Experimental / pathology
Encephalomyelitis, Autoimmune, Experimental / prevention & control*
Female
Immunomodulation / drug effects
Mice
Mice, Inbred C57BL
Microglia / drug effects
Microglia / pathology
Myelin Sheath / drug effects
Myelin Sheath / physiology
Myelin-Oligodendrocyte Glycoprotein / adverse effects
Peptide Fragments / adverse effects
Quetiapine Fumarate
Spinal Cord / drug effects
Spinal Cord / immunology
Spinal Cord / pathology
Spinal Cord / physiopathology

Substances

Antipsychotic Agents
Dibenzothiazepines
Myelin-Oligodendrocyte Glycoprotein
Peptide Fragments
myelin oligodendrocyte glycoprotein (35-55)
Quetiapine Fumarate

Grants and funding

This work is in part supported by the National Natural Science Foundation of China (NSCF, 81071084), International Science & Technology Cooperation Program of China (2010DFB30820) and Natural Science Foundation Project of Chongqing (CQ CSTC, 2009BB5157, 2010BB5157). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.