Cytokine production in drug-free and neuroleptic-treated schizophrenic patients

Tel Aviv University, Tell Afif, Tel Aviv, Israel
Biological Psychiatry (Impact Factor: 10.26). 09/1995; 38(5):297-302. DOI: 10.1016/0006-3223(94)00299-I
Source: PubMed


A line of evidence indicates changes of the immune system in schizophrenic patients. We investigated the production of cytokines by peripheral blood mononuclear cells (PBMCs) in drug-free and neuroleptic-treated schizophrenic patients compared to healthy, normal controls. A significant reduction in interleukin (IL)-2 production was detected in untreated schizophrenic patients (-59.6%; p < .05) as well as in IL-3-like activity (IL-3-LA) production (-27.4%; p < .05) in treated patients compared to controls. No alteration was observed in IL-1 beta production. It seems that schizophrenia is associated with diminished IL-2 production, while neuroleptic treatment interferes with the capacity of immunocompetent cells to synthesize and/or release Il-3-LA. The alteration in cytokine production did not correlate with either the severity of the disorder or the serum prolactin levels.

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    • "In our previous case-control study, statistically significant differences were observed in IL-3 levels between chronic patients and normal controls (Xiu et al., 2008). In contrast, some studies found that IL-3 serum levels were significantly reduced in chronic patients with schizophrenia (Bessler et al., 1995; Dimitrov et al., 2013). Numerous factors may have contributed to these discrepancies, such as differences in testing material (serum vs. plasma) or in the stored period of the sample, exposure for antipsychotic treatment (naive vs. medicated), sampling of patients in different stage of disease progression (acute vs. chronic or active phase vs. remission), illness duration, age at onset, and ethnic origin or genetic background of the population studied. "
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    ABSTRACT: Schizophrenia is associated with the inflammation-related pathways, including aberrant cytokines levels. In this study, we examined the association of serum IL-3 levels with psychopahological symtoms in chronic schizophrenia. Serum IL-3 levels were assessed in 42 patients diagnosed with schizophrenia and compared to 43 healthy control subjects matched for age and gender. Schizophrenia symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS), and serum IL-3 levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Our results showed that IL-3 levels were significantly increased in patients with chronic schizophrenia compared to healthy control subjects. Correlation analysis revealed a significant positive correlation between the IL-3 levels and the PANSS general subscore. Moreover, IL-3 levels were significantly positively correlated with depressive subscore. Our results suggested that IL-3 related pathway is associated with psychopathology of schizophrenia patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    07/2015; 229(1-2). DOI:10.1016/j.psychres.2015.07.029
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    • "Various cytokines have been studied in connection with schizophrenia, but the findings are inconsistent. For example, studies have shown increased levels of IL-6 and tumor necrosis factor (TNF)-α8,20-23) but decreased levels of IL-224,25) in SCP, while others have found no change26,27) in cytokine levels. Moreover, there is contradictory evidence concerning anti-inflammatory cytokines such as IFN-γ, IL-4, and IL-10. "
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    ABSTRACT: We investigated the effects of antipsychotics on immune-challenged peripheral blood mononuclear cell (PBMC) cultures. 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. 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. 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).
    Clinical Psychopharmacology and Neuroscience 12/2013; 11(3):144-51. DOI:10.9758/cpn.2013.11.3.144
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    • "There are two important differences in assay methodology between our study and some of the other published works in the literature. We investigated mitogen-stimulated cytokine production employing purified leukocytes rather than a whole blood assay (Arolt et al, 2000; Bessler et al, 1995; Cazzullo et al, 2002; De Groote et al, 1992; Ganguli et al, 1995; Kim et al, 1998; O&apos;Donnell et al, 1996; Rothermundt et al, 1998; Wilke et al, 1996 "
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    ABSTRACT: Aberrant activation of the immune system has been implicated in an increasingly large number of disease states and can influence cognition, mood, and memory. There is a long and controversial history of reports of immune activation associated with schizophrenia. In this study, we measured mitogen-stimulated cytokine levels serially in 100 medication-stabilized continuously ill subjects with schizophrenia and compared and contrasted them with mitogen-stimulated cytokine levels from 51 normal volunteers. The subjects with schizophrenia had consistently higher mitogen-stimulated IL-2 levels and lower IL-6 levels than the normal volunteers. These effects could not be explained by medications, smoking, or other clinical variables. We conclude that continuously symptomatic medication-stabilized subjects with schizophrenia have a mitogen-stimulated cytokine expression pattern that is suggestive of ongoing immune activation.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 09/2009; 35(2):428-34. DOI:10.1038/npp.2009.145 · 7.05 Impact Factor
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