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Neuroleptics modulate cytokine and reactive oxygen species production in blood leukocytes of healthy volunteers

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Szuster-Ciesielska A., Slotwinska M., Stachura A., Marmurowska-Michalowska H., Kandefer-Szerszen M.

Archivum Immunologiae et Therapiae Experimentalis

2004

vol. 52

issue 1

59-67

There have been several reports indicating that schizophrenia is related to the activation of the inflammatory response system (IRS),characterized by increased serum concentrations of several cytokines,and that antipsychotic drugs may have immunosuppressive or immunoreg- ulatory effects.The aim of the present study was to examine the effects of neuroleptics on cytokine and reactive oxygen species production in vitro,in blood leukocytes. We studied the effect of haloperidol,chlorpromazine and clozapine on the unstimulated and stimulated (phytohemagglutinin+lipopolysaccharide ?PHA+LPS)production of some cytokines which are known to be mainly products of T lymphocytes and monocytes (IL-2, lymphotoxin,IFN-? ,IL-12,IL-4,IL-10 and TGF-? )in peripheral blood mononuclear cells (PBMC)of healthy subjects.We also compared the effect of neuroleptics on superoxide anion and hydrogen peroxide production in blood neutrophils. All three antipsychotic drugs significantly increased PHA+LPS-stimulated production of anti-inflammatory cytokines such as IL-10 and TGF-? as well as unstimulated production of IL-10,but they did not influence IL-12 production.In the same in vitroconditions they inhibited PHA+LPS-stimulated production of IL-2 and lymphotoxin.IL-4 production was inhibited by haloperidol and chlorpromazine,but not by clozapine.IFN-? production was inhibited by haloperidol and chlorpromazine,but stimulated by clozapine.All neuroleptics examined at a high (100 muM)concentration,but not at a 1 muM concentration,significantly inhibited superoxide anion production by phorbol ester (PMA)-stimulated neutrophils in vitro. The results indicate that in vitro typical antipsychotic drugs, such as haloperidol and chlor- promazine, and atypical ones, such as clozapine, modulate cytokines which are known to be produced by monocytes as well as by T helper (Th)1 and Th2 subpopulations.

Investigation of serum cytokine levels and cytokine production in whole blood cultures of paranoid schizophrenic patients

100%

Kaminska T., Wysocka A., Marmurowska-Michalowska H., Dubas-Slemp H., Kandefer-Szerszen M.

Archivum Immunologiae et Therapiae Experimentalis

2001

vol. 49

issue 6

439-446

There is some evidence that the pathophysiology of schizophrenia is related to changes in the innate and adaptive immune systems. In an attempt to define a potential immunological dysfunction in schizophrenia, we measured the serum levels of several cytokines in the sera of 24 patients with paranoid schizophrenia and investigated the cytokine production in whole blood assays after stimulation in vitro with virus (Newcastle disease), phytohemagglutinin (PHA) or bacterial lipopolysaccharide (LPS) and compared them with healthy, normal controls. A significant increase of IL-6, IL-8 and IFN- gamma levels, but a decreased IL-10 level were observed in the sera of patients with schizophrenia. No significant changes in the serum levels of IL-2, IL-4, IFN-alpha and TNF-alpha were detected in these patients. When cytokine production in vitro was examined, a significant defect in PHA-induced IL-2, IL-4 and IFN-gamma, and in virus-induced IFN-alpha production, but no significant alterations in LPS-induced IL-6, IL-10 and TNF-alpha production were observed. In summary, increased serum levels of some cytokines such as IL-6, IL-8 and IFN-gamma indicate an activation of the inflammatory response in schizophrenia, while the in vitro assay indicates significant changes in the Th1 (decreased production of IL-2 and IFN-gamma) and Th2 (decreased production of IL-4) cell system responses. The role of the defective IFN-apha production in the regulation of the imbalance between Th1 and Th2 cell system responses is suggested.

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2 Archivum Immunologiae et Therapiae Experimentalis

1 2004

1 2001

2 Kandefer-Szerszen M.

2 Marmurowska-Michalowska H.

1 Dubas-Slemp H.

1 Kaminska T.

1 Slotwinska M.

1 Stachura A.

1 Szuster-Ciesielska A.

1 Wysocka A.

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Neuroleptics modulate cytokine and reactive oxygen species production in blood leukocytes of healthy volunteers

Investigation of serum cytokine levels and cytokine production in whole blood cultures of paranoid schizophrenic patients