Antipsychotic drugs suppress the AKT/NF-κB pathway and regulate the differentiation of T-cell subsets

Abstract: Antipsychotic drugs (APDs) are commonly used to ease the symptoms of schizophrenia; however, these same drugs also have an effect on the human immune system. Our previous studies have shown that risperidone and clozapine effectively decrease the production of IFN-γ for CD4+ T-cells in PBMC. In contrast, haloperidol causes an increase in the production of IFN-γ for CD4+ T-cells in PBMC. In this study we show that risperidone and clozapine can reduce Th1 cell differentiation and T-bet expression. The differentiation of Th1 cells was reduced in clozapine or risperidone treated PBMC by inhibiting the phosphorylation of AKT but not STAT-4. Typical APD, haloperidol, had the opposite effect in regulating T cell differentiation when compared with atypical APDs including risperidone and clozapine. Haloperidol decreased the expression of GATA-3, a Th2-related transcription factor, by inhibiting NF-κB activation rather than STAT-6 phosphorylation and thus decreased Th2 differentiation. In addition, chronic risperidone and clozapine treatment reduces the IFN-γ producing CD4+ T-cell population within PBMC. In conclusion, this study suggests that APDs do indeed regulate the body''s immune response and therefore all APDs should have their own patent in regulating immune responses. [Copyright &y& Elsevier]