Decreased Production of Interleukin‐2 in Schizophrenia

Villemain, F.; Chatenoud, Lucienne; Guillibert, E.; Pélicier, Y; Bach, Jean‐François

doi:10.1111/j.1749-6632.1987.tb35828.x

Cited by 46 publications

(8 citation statements)

References 14 publications

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“…Our results confirm the association between acute schizophrenia and low IL-2 production, [8][9][10][11][12][13][14][15] but also clearly confirm our earlier results 30 which showed a decreased IFN-␥ production in acute schizophrenia. Deficient lymphocyte productions of both IL-2 and IFN-␥ were also found throughout the time period of clinical remission, which were also significantly intercorrelated with one another at all three time-points of the investigation.…”

Section: Discussionsupporting

confidence: 82%

“…Six different groups, including our own, have independently demonstrated that mitogen stimulated IL-2 production by peripheral blood mononuclear cells (PBMC) is decreased in patients with schizophrenia. [8][9][10][11][12][13][14][15] This is the most frequently confirmed finding in the immunology of schizophrenia and there has not as yet been a failure in demonstrating this phenomenon. In the cerebrospinal fluid (CSF) of drug-free patients, increased levels of IL-2 were found 16 and also significantly predicted the recurrence of psychotic symptoms in relapse-prone schizophrenics.…”

Section: Introductionmentioning

confidence: 99%

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Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment

et al. 2000

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A pattern of aberrations in the T-cell cytokine system that is typical for autoimmune disorders has also been reported in patients with schizophrenia, namely a decreased interleukin-2 (IL-2) production and increased levels of the soluble IL-2 receptor (sIL-2R). It has also been reported that the production of interferon-␥ (IFN-␥) may be lowered. In a longitudinal design, we studied the production of both IFN-␥ and IL-2 and their correlation in patients with schizophrenia during treatment and investigated whether associations exist between cytokine production and clinical variables. The production of IFN-␥ and IL-2 was measured in equal numbers (n = 29) of patients with schizophrenia (DSM-IV) and controls who were matched for age and gender. Patients were measured 1 day after admission (T1), after 14 (T2) and 28 (T2) days of treatment. Psychopathology was assessed after these times. The production of both IFN-␥ and IL-2 was significantly lower in patients than in controls throughout the whole investigation period (T1-T3). The productions of both cytokines were significantly correlated in controls (r = 0.60, P Յ 0.001) as well as in patients with schizophrenia (mean production T1-T3: r = 0.71, P Յ 0.001). No associations between cytokine measurements and psychopathology or age-at-onset could be found. Our findings of lowered and correlated IFN-␥ and IL-2 production indicate that alterations in the cytokine system of patients with schizophrenia might resemble those in autoimmune disorders. It is suggested that these immunological abnormalities are associated with acute exacerbation, rather than with a clinical subtype of schizophrenia. Molecular Psychiatry (2000) 5, 150-158.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment

et al. 2000

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“…Moreover, the copolymer glatiramer acetate (copolymer-1, Cop-1), a weak agonist of self-antigens, leads to the activation of T suppressor cells that can counteract the psychotomimetic effects of dizolcipine maleate (MK-801) and amphetamine (21). Overexpression of Egr2 and Egr3 has been shown to inhibit the transcription of IL-2 (20,22), and altered IL-2 regulation has been reported in schizophrenia (23,24). In addition to their downstream position in calcineurin signaling, EGR genes interact with a number of other factors implicated in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3 , as potential susceptibility candidates in schizophrenia

Yamada¹,

Gerber

Iwayama³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

149

133

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The calcineurin cascade is central to neuronal signal transduction, and genes in this network are intriguing candidate schizophrenia susceptibility genes. To replicate and extend our previously reported association between the PPP3CC gene, encoding the calcineurin catalytic ␥-subunit, and schizophrenia, we examined 84 SNPs from 14 calcineurin-related candidate genes for genetic association by using 124 Japanese schizophrenic pedigrees. Four of these genes (PPP3CC, EGR2, EGR3, and EGR4) showed nominally significant association with schizophrenia. In a postmortem brain study, EGR1, EGR2, and EGR3 transcripts were shown to be downregulated in the prefrontal cortex of schizophrenic, but not bipolar, patients. These findings raise a potentially important role for EGR genes in schizophrenia pathogenesis. Because EGR3 is an attractive candidate gene based on its chromosomal location close to PPP3CC within 8p21.3 and its functional link to dopamine, glutamate, and neuregulin signaling, we extended our analysis by resequencing the entire EGR3 genomic interval and detected 15 SNPs. One of these, IVS1 ؉ 607A3 G SNP, displayed the strongest evidence for disease association, which was confirmed in 1,140 independent case-control samples. An in vitro promoter assay detected a possible expression-regulatory effect of this SNP. These findings support the previous genetic association of altered calcineurin signaling with schizophrenia pathogenesis and identify EGR3 as a compelling susceptibility gene.genetic association ͉ immediate early gene ͉ postmortem brain ͉ enhancer

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“…They conclude that acutely ill patients with schizophrenia have TH-2 immune activation that resolves with treatment (Müller and Schwarz, 2006b). In general, studies of mitogen-stimulated cytokine levels from acutely ill individuals with schizophrenia report decreased interluken-2 (IL-2) production which could be interpreted as being consistent with the aforementioned hypothesis (Arolt et al, 2000; Bessler et al, 1995; Cazzullo et al, 2002; Cazzullo et al, 2001; Ganguli et al, 1995; Ganguli et al, 1989; Kim et al, 2001; Kim et al, 2004; Potvin et al, 2008; Rothermundt et al, 2000; Villemain et al, 1987). …”

Section: Introductionmentioning

confidence: 68%

Serial Mitogen-Stimulated Cytokine Production from Continuously Ill Patients with Schizophrenia

Rapaport

Bresee

2009

Neuropsychopharmacol

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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.

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Decreased Production of Interleukin‐2 in Schizophrenia

Cited by 46 publications

References 14 publications

Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment

Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment

Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3 , as potential susceptibility candidates in schizophrenia

Serial Mitogen-Stimulated Cytokine Production from Continuously Ill Patients with Schizophrenia

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