Mitogen-Stimulated Interleukin-2 Production in Never-Medicated, First-Episode Schizophrenic Patients

Ganguli, Rohan; Brar, Jaspreet S.; Chengappa, K. N. Roy; DeLeo, M.; Yang, Zhenlin; Shurin, Galina V.; Rabin, Bruce S.

doi:10.1001/archpsyc.1995.03950200058014

Cited by 120 publications

(36 citation statements)

References 29 publications

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“…Cross-sectional studies have shown that negative symptoms of schizophrenia were significantly negatively correlated with both increased soluble IL-2-receptor concentration 66 and lowered IL-2 production in non-medicated schizophrenics. 67 In the latter study, a highly significant positive correlation was found between age-of-onset and IL-2 production. This is particularly important, since it suggests an association between lowered IL-2 production and the structural brain abnormalities which are supposed to be associated with these clinical features.…”

Section: Production Of: Il-2 (T1) Il-2 (T2) Il-2 (T3) Ifn-␥ (T1) Ifn-mentioning

confidence: 71%

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: Production Of: Il-2 (T1) Il-2 (T2) Il-2 (T3) Ifn-␥ (T1) Ifn-mentioning

confidence: 71%

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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“…Recently, studies have shown that the interface between these complex systems is impaired in schizophrenia (SCH, Altamura et al, 1999). Specially, SCH has been associated with several immunological abnormalities, including decreased mitogen-induced lymphocyte proliferation , altered numbers of total T and T-helper cells (Muller et al, 1993), the presence of antibrain antibodies in serum (Henneberg et al, 1994), and changes in cytokines and cytokine receptors in the blood and the cerebrospinal fluid (CSF) (Licinio et al, 1993;Rapaport et al, 1994Rapaport et al, , 1997Ganguli et al, 1994Ganguli et al, , 1995Maes et al, 1995Maes et al, , 1997Maes et al, , 2000Maes et al, , 2002Lin et al, 1998;Arolt et al, 2000;Zhang et al, 2002a, b). Together, these studies show that SCH is associated with significant immunological alterations, and activation of the inflammatory response system (IRS) is mediated, in part, by cytokines.…”

Section: Introductionmentioning

confidence: 99%

Cortisol and Cytokines in Chronic and Treatment-Resistant Patients with Schizophrenia: Association with Psychopathology and Response to Antipsychotics

Zhang

Zhou

Cao

et al. 2005

Neuropsychopharmacol

178

110

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The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic-pituitary-adrenal (HPA) axis to the stimulatory influence of cytokines and stress-related mediators. Growing evidence suggests that neuro-immune-endocrine crosstalk may be impaired in schizophrenia. We determined the relationship between cortisol, cytokines interleukin-2 (IL-2) and interleukin-6 (IL-6), and symptoms in schizophrenia during treatment with typical and atypical antipsychotic drugs. Subjects included 30 healthy controls (HC) and 78 schizophrenic (SCH) in-patients. SCH were randomly assigned to 12-week treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). Serum cortisol and IL-2 levels were assayed by radioimmunometric assay, and serum IL-6 levels by quantitative enzyme-linked immunosorbent assay. Following a 2-week washout period, serum levels of cortisol, IL-2, and IL-6 were increased in patients with schizophrenia compared to HC. Elevations in cortisol were associated with increase in both IL-2 and IL-6 in SCH. Moreover, elevations in cortisol were associated with negative symptoms and IL-2 with positive symptoms. In all, 12 weeks of risperidone treatment significantly decreased elevated cortisol and improved negative symptoms, but produced similar effects on IL-2 and IL-6 as well as on positive symptoms compared to haloperidol. The improvement of negative symptoms was related to the change in cortisol. Our results suggest that the imbalance in the HPA axis and cytokine system in patients with SCH is implicated in clinical symptoms, and is improved with atypical antipsychotic treatment.

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“…6 The innate immune activation in schizophrenia has been based on the findings of increased monocyte numbers, increased activity of macrophage, increased proinflammatory cytokine levels such as IL-1, IL-6, IL-18 and tumor necrosis factor(TNF)-␣. [7][8][9][10][11] Schizophrenia is also characterized by a decrease in IL-2 production [12][13][14] and interferon(IFN)-␥, 7,15 traditionally classified as Th1 cytokines, and an increase in IL-4 16 and IL-10, 17,18 traditionally classified as Th2 cytokines. On the other hand, there have been reports of an increased Th1 system in schizophrenia, specifically an increased IL-2 level in plasma 19 and in cerebrospinal fluid 20,21 and increased production of IL-2 and IFN-␥.…”

Section: Introductionmentioning

confidence: 99%

The plasma levels of interleukin-12 in schizophrenia, major depression, and bipolar mania: effects of psychotropic drugs

et al. 2002

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Interleukin-12 (IL-12) plays a key role in promoting T helper 1 (Th1) responses and subsequent cell-mediated immunity. Given the role of cytokines in the pathogenesis of psychiatric disorders, the dysregulation of IL-12 in these illnesses would be expected. We measured the plasma levels of IL-12 in 102 psychiatric patients (43 schizophrenia, 34 major depression and 25 bipolar disorder) and 85 normal controls. In addition, IL-12 levels of the patients were measured after an 8-week treatment to assess whether the levels were affected by medication. The IL-12 levels of the patient group with major depression were significantly higher than that of the control group, whereas no differences were found among the other groups. IL-12 values of the three patient groups decreased significantly after 8 weeks of treatment. These findings support the hypothesis that activation of the inflammatory response system and in particular of Th-1-like cells, is involved in the pathophysiology of major depression and that repeated administration of antidepressive and antipsychotic drugs may suppress IL-12 plasma concentrations in psychiatric patients.

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Mitogen-Stimulated Interleukin-2 Production in Never-Medicated, First-Episode Schizophrenic Patients

Abstract: Our finding of low IL-2 production in neuroleptic-native schizophrenic patients confirms that this finding is not confounded by medications. The correlation of low IL-2 production with younger age at onset suggests that this may be a marker for a subtype of the illness or for severity.

Cited by 120 publications

References 29 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

Cortisol and Cytokines in Chronic and Treatment-Resistant Patients with Schizophrenia: Association with Psychopathology and Response to Antipsychotics

The plasma levels of interleukin-12 in schizophrenia, major depression, and bipolar mania: effects of psychotropic drugs

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