Quetiapine, an atypical antipsychotic, is protective against autoimmune-mediated demyelination by inhibiting effector T cell proliferation.
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.
Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, China.
Feng
F
Mei
Sheng
S
Guo
Yangtao
Y
He
Linyun
L
Wang
Hongkai
H
Wang
Jianqin
J
Niu
Jiming
J
Kong
Xinmin
X
Li
Yuzhang
Y
Wu
Lan
L
Xiao
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D056747:Immunomodulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000009:adverse effects; D010446:Peptide Fragments / Q000009:adverse effects; D000069348:Quetiapine Fumarate; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D000069348:Quetiapine Fumarate