Decreased Interleukin-2 Production in Korean Schizophrenic Patients

{ "0" : "Department of Psychiatry, College of Medicine, Korea University, Seoul, South Korea." , "2" : "Schizophrenia" , "3" : "interleukin" , "4" : "autoimmune hypothesis" , "5" : "ethnicity"}
Biological Psychiatry (Impact Factor: 10.26). 05/1998; 43(9):701-704. DOI: 10.1016/S0006-3223(97)00357-0


Background: It has been postulated that autoimmune process may play a role in the pathogenesis of symptoms in some schizophrenic patients. Findings of altered interleukin (IL) regulation have been regarded as additional proof that schizophrenia has an autoimmunological background.Methods: Sixteen patients who fulfilled DSM-IV criteria for schizophrenia and who were drug free for at least six months and the same number of age- and sex-matched controls were recruited. The severity of symptoms in schizophrenia was assessed by BPRS. Phytohemagglutinin (PHA)-stimulated production and serum level of IL-1β, IL-2, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA).Results: There was a significant decrease of IL-2 production (p < .01) in schizophrenic patients and a significant increase of IL-2 serum level (p < .01). No significant difference of IL-1β and IL-6 was found. Some patients and controls had measurable serum level of IL-1β and IL-6. No significant correlation between production and serum level of IL-1β, -2, -6 and age, duration of illness, and BPRS score in schizophrenics was found.Conclusions: This is the first study to describe a decrease of IL-2 production and increase of IL-2 serum level in non-Caucasian schizophrenic patients. These findings are further evidence that autoimmune process is present, regardless of ethnic origin, in some schizophrenic patients.

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Available from: Yong-Ku Kim, Oct 09, 2014
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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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    • "Changes in cytokines and cytokine receptors have been reported in plasma, serum, and cerebrospinal fluid (CSF) of schizophrenic patients, such as increased IL-6, IL-1β, and TNFα (Shintani et al 1991; Ganguli et al 1994; Xu et al 1994; Maes et al 1995; Naudin et al 1996; Frommberger et al 1997; Monteleone et al 1997; Lin et al 1998; van Kammen et al 1999; Theodoropoulou et al 2001; Zhang et al 2002; Garver et al 2003). However, results are inconsistent (Baker et al 1996; Kim et al 1998; Haack et al 1999; Kudoh et al 2001), but several investigations have shown a relationship between IL-6 and negative symptoms, duration of the disease (Ganguli et al 1994; Akiyama 1999; Kim et al 2000), acute state of the disorder (Frommberger et al 1997), and treatment resistance (Lin et al 1998). These findings suggest that high IL-6 levels are associated with an unfavorable course of the disease (Müller et al 2000). "
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    ABSTRACT: In schizophrenia, alterations of proinflammatory cytokine levels have been reported and related to the disease and psychopathology. However, only limited conclusions can be drawn in view of confounding factors such as infection, age, sex, smoking, and antipsychotic medication. Chronic schizophrenic patients with a long-term disease process and medication period have not been investigated so far. We have measured serum levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)alpha in 41 elderly, chronic schizophrenic patients and 23 age- and sex-matched controls using enzyme-linked immunosorbent assay (ELISA). We assessed detailed psychopathology and neuropsychological performance and determined serum levels of haloperidol, clozapine, and the two main clozapine metabolites, desmethylclozapine and clozapine metabolite N-oxide, by high-pressure liquid chromatography (HPLC). IL-1beta and IL-6 levels were increased in treatment-resistant schizophrenic patients compared with healthy controls, whereas TNFalpha showed no difference. We did not find statistically significant differences of cytokine levels between medication groups and there was no correlation with serum levels of antipsychotics or psychopathological rating scores. Elevations of IL-1beta and IL-6 in elderly chronic schizophrenic patients may be related to an active disease process lasting until old age. Despite missing correlations, long-term treatment effects in treatment-resistant patients may have affected TNFalpha, leading to control levels. Post-mortem and animal studies should clarify the presence of altered immune function in the brain as well as the effect of cytokine levels in relation to neurodevelopmental disturbances and schizophrenia-associated behavior.
    Neuropsychiatric Disease and Treatment 07/2005; 1(2):171-7. DOI:10.2147/nedt. · 1.74 Impact Factor
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    • "Following the observation by Dvorakova et al. (1980) that there were relationship between endogenous psychoses and T and B lymphocytes, research has been directed to studies of lymphocyte activities (Muller et al., 1987), change in plasma cytokines (Villemain et al., 1987) and presence of cytokines in the brain (Breder et al., 1988) in late 1980s. Circumstantial evidences suggested that schizophrenia is associated with dysregulation of immune mediators (Akiyama, 1999; Ganguli et al., 1994; Hornberg et al., 1995; Kim et al., 1998; O'Donnell et al., 1996; Wilke et al., 1996). However, the changes of Th1 cytokines IL-2 and TNF-a in schizophrenia showed controversial findings in different studies (Akiyama, 1999; Cazzullo et al., 2001; DeLisi, 1996; Ganguli et al., 1992; Gattaz et al., 1992; Kim et al., 2000, 2002; Maes et al., 1995; Naudin et al., 1997; O'Donnell et al., 1996; Theodoropoulou et al., 2001). "
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    ABSTRACT: Several studies have shown that there is an imbalance between T helper 1 (Th1) cytokines and T helper 2 (Th2) cytokines in patients with schizophrenia. The T helper 3 (Th3) cytokine, transforming growth factor beta-1 (TGF-beta1), has been shown to suppress the production of Th1 cytokines. Therefore it is hypothesized that it may play a role in schizophrenia by suppressing overactive Th1 system. We recruited 88 schizophrenic patients and 88 matched controls. The basal plasma concentrations of IFN-gamma (Th1), IL-4 (Th2) and TGF-beta1 (Th3) were studied at the time the patients were admitted to the hospital and following 8 weeks of treatment with antipsychotics. The detection rate of plasma IFN-gamma and basal plasma TGF-beta1 level were significantly higher in schizophrenic patients than in controls whereas detection rate of plasma IL-4 was lower in patients. The ratio of Th1/Th2 cytokines (IFN-gamma/IL-4) was higher in schizophrenic patients. Following the neuroleptic treatment, the IFNgamma and TGF-beta1 levels returned to control values, and IL-4 concentration rose above the control value. Schizophrenic patients showed higher Th1/Th2 ratio which is attenuated by effective neuroleptic treatment. It is possible that TGF-beta1 plays a role in reducing the activity of Th1 cytokine.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2004; 28(7):1129-34. DOI:10.1016/j.pnpbp.2004.05.047 · 3.69 Impact Factor
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