title: Clozapine inhibits Th1 cell differentiation and causes the suppression of IFN-γ production in peripheral blood mononuclear cells.
abstract: Antipsychotic drugs (APDs) are widely used to alleviate a number of psychic disorders and may have immunomodulatory effects. However, the previous studies of cytokine and immune regulation in APDs are quite inconsistent. The aim of this study was to examine the in vitro effects of different ADPs on cytokine production by peripheral blood mononuclear cells (PBMCs). We examined the effects of risperidone, clozapine, and haloperidol on the production of phorbol myristate acetate and ionomycin-induced interferon-γ (IFN-γ)/interleukin (IL)-4 in PBMCs by using intracellular staining. Real-time quantitative PCR and Western blot were used to further examine the expression changes of some critical transcription factors related to T-cell differentiation in antipsychotic-treated PBMCs. Our results indicated that clozapine can suppress the stimulated production of IFN-γ by 30.62%, whereas haloperidol weakly enhances the expression of IFN-γ. Differences in IL-4 production or in the number of CD4+ T cells were not observed in cells treated with different APDs. Furthermore, clozapine and risperidone inhibited the T-bet mRNA and protein expression, which are critical to Th1 differentiation. Also, clozapine can enhance the expression of Signal Transducer and Activator of Transcription 6 and GATA3, which are critical for the differentiation of Th2 cells. The results suggested that clozapine and haloperidol may induce different immunomodulatory effects on the immune system.
authors.affiliation: Department of Research, Buddhist Tzu Chi General Hospital, Taipei Branch, New Taipei City, Taiwan.
authors.forename: Mao-Liang
authors.initials: ML
authors.lastname: Chen
authors.forename: Tzung-Chieh
authors.initials: TC
authors.lastname: Tsai
authors.forename: Lu-Kai
authors.initials: LK
authors.lastname: Wang
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Lin
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Tsai
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Lee
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Tsai
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D003024:Clozapine / Q000494:pharmacology*; D050990:GATA3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D050800:STAT6 Transcription Factor / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C508598:IL4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4; D007371:Interferon-gamma; D003024:Clozapine; D006220:Haloperidol