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.


Available from: Yong-Ku Kim, Oct 09, 2014
  • Source
    • "Pro-inflammatory cytokines produced by chronically activated macrophages and T-lymphocytes have been reported as immunological findings in schizophrenia (Smith and Maes, 1995). Subsequent studies suggested that Th1 cytokines such as interleukin-2 (IL-2) and interleukin-12 (IL-12) are decreased in schizophrenia (Kim et al., 1998), whereas Th2 cytokines such as interleukin-10 (IL-10) are increased (Kim et al., 2002; Maes et al., 2002). Based on the dichotomous concept of an adaptive immune response, the Th1/Th2 imbalance hypothesis was suggested (Schwarz et al., 2001). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning. Although novel antipsychotics have been developed, the negative and cognitive symptoms of schizophrenia are still unresponsive to pharmacotherapy. The high level of social impairment and a chronic deteriorating course suggest that schizophrenia likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological factors for psychiatric disorders, including schizophrenia. Inflammation in the central nervous systemis closely related to neurodegeneration. In addition to pro-inflammatory cytokines, microglia also play an important role in the inflammatory process in the CNS. Uncontrolled activity of pro-inflammatory cytokines and microglia can induce schizophrenia in tandem with genetic vulnerability and glutamatergic neurotransmitters. Several studies have investigated the possible effects of antipsychotics on inflammation and neurogenesis. Additionally, anti-inflammatory adjuvant therapy has been under investigation as a treatment option for schizophrenia. Further studies should consider the confounding effects of systemic factors such as metabolic syndrome and smoking. In addition, the unique mechanisms by which pro-inflammatory cytokines are involved in the etiopathology of schizophrenia should be investigated. In this article, we aimed to review(1) major findings regarding neuroinflammation and pro-inflammatory cytokine alterations in schizophrenia, (2) interactions between neuroinflammation and neurogenesis as possible neural substrates for schizophrenia, and (3) novel pharmacological approaches.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2015; DOI:10.1016/j.pnpbp.2015.06.008 · 3.69 Impact Factor
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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
Show more