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Objective: We investigated the effects of antipsychotics on immune-challenged peripheral blood mononuclear cell (PBMC)cultures. Methods: Blood samples were collected from twelve patients with first-episode schizophrenia. The PBMCs were separated and cultures were prepared and stimulated with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly[I:C]), and then separately treated with a typical antipsychotic (haloperidol) or atypical antipsychotic (clozapine, quetiapine, or risperidone). Pro-inflammatory (interferon gamma [IFN-γ]) and anti-inflammatory (interleukin [IL]-4 and IL-10) cytokine levels were measured in the LPS- or poly(I:C)-stimulated PBMC cultures treated with antipsychotics. Results: Haloperidol and quetiapine significantly increased the IL-4 levels (p<0.05) in LPS-stimulated PBMC cultures, while clozapine and quetiapine significantly enhanced the IL-4 levels (p<0.05) in poly(I:C)-stimulated PBMC cultures. Only treatment with haloperidol resulted in a significant increase in IL-10 production (p<0.05) in LPS-stimulated PBMC cultures, whereas clozapine,quetiapine, and risperidone treatment significantly increased IL-10 production (p<0.05) in poly(I:C)-stimulated PBMC cultures. All of the antipsychotics reduced the IFN-γ level significantly (p<0.05) in LPS- and poly(I:C)-stimulated PBMC cultures. Conclusion: Antipsychotic treatment altered immune function by raising the levels of anti-inflammatory cytokines (IL-4 and IL-10)and suppressing the levels of pro-inflammatory cytokines (IFN-γ).

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