Immunosuppressive effects of clozapine and haloperidol: enhanced production of the interleukin-1 receptor antagonist

In schizophrenic patients, multiple immune abnormalities have been reported, including increased production of proinflammatory cytokines. There is some evidence that antipsychotic drugs may have immunosuppressive effects. The aim of this study was to examine the in-vitro effects of different concentrations of antipsychotic agents on cytokine production by human whole blood. We examined the effects of clozapine and haloperidol, 10(-4), 10(-6) and 10(-8)M, on the unstimulated and stimulated (lipopolysaccharide+phytohemagglutinin) production of interleukin-6 (IL-6), IL-10, interferon-gamma (IFNgamma), and the IL-1 receptor antagonist (IL-1RA). Clozapine, 10(-6) and 10(-8)M, and haloperidol, 10(-4), 10(-6), and 10(-8)M, significantly increased the unstimulated and stimulated production of IL-1RA. Clozapine 10(-6)M significantly increased the stimulated production of IFNgamma. Clozapine 10(-4)M significantly suppressed the unstimulated production of IL-6 and IL-1RA and the stimulated production of IL-6, IL-10, IFNgamma and IL-1RA. The results suggest that both clozapine and haloperidol, at concentrations within the therapeutic range, may exert immunosuppressive effects through an enhanced production of IL-1RA.