In-vitro Immunomodulatory Effects of Haloperidol and Perazine in Schizophrenia

Abstract

There are some reports describing concurrent changes in lymphocytic and monocytic activities in schizophrenia. In this study we investigated T cell activity in schizophrenic patients by measuring the release of interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) by T cells and the percentages of CD4+ and CD8+ cells in blood. The release of IL-2 and sIL-2R by T cells was evaluated in dilute whole blood after in-vitro stimulation with phytohemagglutinin. IL-2 levels and the percentage of CD4-cells tended to decrease and sIL-2R levels decreased significantly in schizophrenic patients. Haloperidol and perazine significantly decreased IL-2 levels and increased sIL-2R levels and the percentage CD4-cells. IL-2 and sIL-2R levels were lower in patients with a predominance of positive symptoms. The neuroleptic-induced increase in sIL-2R levels was higher in patients with a predominance of positive symptoms compared with those in whom both positive and negative symptoms were severe. The study has shown that T-cell activity is reduced in schizophrenia and that neuroleptics may have immunomodulatory properties.

Effects of Antipsychotics on the Inflammatory Response System of Patients with Schizophrenia in Peripheral Blood Mononuclear Cell Cultures

“…Haloperidol seems to normalize increased IL-2 plasma and serum levels37) and inhibit mitogen-stimulated IL-2 production in PBMCs 38,39). The effects of haloperidol are particularly evident in patients with positive symptoms 51). Haloperidol lowers TNF-α production in LPS-stimulated monocytes,52) but does not affect the IL-6 concentration in serum, plasma,37,53,54) or CSF55) from SCP.…”

Schizophrenia, autoimmunity and immune system dysregulation: A comprehensive model updated and revisited

“…Increased levels [22] Especially in younger patients [24] Acute psychosis [23,24] Poor prognosis [102] Lower in positive symptoms [102] First degree relative [24] Tardive dyskinesia [23] IL-4 Increased CSF levels [30] e IL-6 Increased levels [18] Younger age [19] Illness duration [20] Acute exacerbation [103] Negative symptoms [104] Neuroleptic malignant syndrome [105] Delayed responders [18] Treatment resistance [18] Soluble IL-6 receptor Increased levels Paranoid symptomatology [2] IL-10 Increased levels [29] Decrease in levels after treatment [19] TNFa Increased levels [6,98] Negative symptoms [106] Neuroleptic malignant syndrome [105] Interferon-g Decreased mitogen stimulated levels [27] e IL, interleukin; TNF, tumor necrosis factor; CSF, cerebrospinal fluid.…”

Interleukin-10 gene promoter polymorphism in patients with schizophrenia in a region of East Turkey

“…Recently, there has been renewed interest in cytokine genes because of more consistent findings of elevated interleukin-10 (IL-10), interleukin-6 (IL-6) and tumor necrosis factora (TNF-a) with decreased interleukin-2 (IL-2) and interferon-g, indicating predominance of cytokines stimulating the T-helper 2 (Th2) response over Thelper 1 (Th1) cytokines among schizophrenia patients (Kowalski et al 2000;Mü ller et al 2000;He et al 2006;Shirts et al 2006). These observations suggest that the Th1/Th2 imbalance is associated with schizophrenia, and that IL-10, the product of Th2, which has been demonstrated to selectively inhibit cytokine production by Th1 cells as IL-2, interferon (IFN)-g, might be involved in the aetiology of schizophrenia (Kowalski et al 2000;Yu et al 2004;Ozbey et al 2008). …”