Impact of antipsychotics on cytokine production in-vitro

Objective: A growing body of data from genetic, immunological and clinical studies indicates an involvement of the immune system in the pathophysiology of schizophrenia and suggests that the modulation of the cytokine system by antipsychotics may be one cause for the improvement of psychotic symptoms. However, the influence of the typical antipsychotics chlorpromazine and haloperidol, and the effect of typical and atypical antipsychotics on the TSST-1-stimulated blood cell secretion of cytokines, and specifically the interleukin (IL)-17 production have not been studied so far, although IL-17 is a leading pro-inflammatory cytokine. Method: We measured levels of IL-1 beta, IL-2, 1L-4, IL-6, IL-17 and tumor necrosis factor-alpha (TNF-alpha) in stimulated blood of 10 healthy female subjects in a whole blood assay using the toxic shock syndrome toxin TSST-1 as stimulant. Blood was either supplemented with antipsychotics (chlorpromazine, haloperidol, clozapine, N-desmethylclozapine and quetiapine with four different concentrations each) or not. Results: Under TSST-1 stimulation, antipsychotics as a group had no influence on IL-1 beta or IL-6 concentrations but increased IL-4 levels. The most consistent findings were seen regarding IL-17. Mean IL-17 concentrations differed significantly between blood with and without antipsychotic supplements and were increased over all antipsychotics and almost all of the applied antipsychotic concentrations. TNF-alpha levels were increased by chlorpromazine; N-desmethylclozapine and quetiapine reduced IL-2 production. Conclusions: Antipsychotics might, among other mechanisms, act as such by increasing the production of IL-17. (C) 2011 Elsevier Ltd. All rights reserved.