Decreased Interleukin-2 Production in Korean Schizophrenic Patients

Kim, Yong Ku; Lee, Min Soo; Suh, Kwang Yoon

doi:10.1016/s0006-3223(97)00357-0

Cited by 60 publications

(28 citation statements)

References 17 publications

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“…Cytokine abnormalities that have been replicated in studies of schizophrenic patients include increased serum-soluble interleukin-2 receptors (Maes et al 1995;Akiyama 1999) and serum IL-6 levels (Ganguli et al 1994;Maes et al 1995;Akiyama 1999). Contradictory results have been reported on IL-2 serum levels (Gattaz et al 1992;Kim et al 1998). Thus, in the present study, sensorimotor gating deficient LPSexposed rats displayed, to some extend, similar immune alterations as those reported in schizophrenic patients.…”

Section: Discussionsupporting

confidence: 83%

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

Borrell

Vela²,

Arévalo-Martı́n³

et al. 2002

Neuropsychopharmacology

280

191

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Increasing evidence associates schizophrenia with prenatal exposure to infection. Impaired ability to "gate out" sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition (PPI) of the acoustic startle reflex. We analyzed the effect of a prenatal immune challenge-peripheral administration of bacterial endotoxin lipopolysaccharide (LPS) to pregnant female rats-upon PPI and immune function in adult offspring. Prenatal LPS treatment disrupted PPI which was reversed by antipsychotics. Serum levels of interleukin-2 and interleukin-6 were increased. In addition, histopathological features in brain areas related with PPI circuitry were observed. These results illustrate the critical influence of prenatal immune events upon adult CNS functioning in association with the putative role of the immune system in (Braff et al. 1978;Kumari et al. 1999). A well-established sensorimotor gating paradigm is the prepulse inhibition (PPI) of the startle response. PPI refers to the reduction in startle reactivity toward an intense pulse stimulus when it is shortly preceded by a weak prepulse stimulus (Hoffman and Ison 1980). It is thought that the prepulse response activates an inhibitory process that attenuates or "gates" the startle response. Because identical stimulus parameters can be used for animal and human studies, it is considered that animal models of PPI disruption represent a promising way to study the neural mechanisms underlying sensorimotor gating dysfunction (Swerdlow et al. 1994(Swerdlow et al. , 1999Swerdlow and Geyer 1998) and as a screening test for potential antipsychotics (Swerdlow et al. 1994;Depoortere et al. 1997). In fact, antipsychotics remove PPI deficits in schizophrenic patients (Kumari et al. 1999;Weike et al. 2000). Nevertheless, it must be taken into consideration that deficiency of PPI has been reported in other selected neuropsychiatric disorders where inability to inhibit movements is involved (Huntington's disease (Swerdlow et al. 1995 Tourette's syndrome (Castellanos et al. 1996)), where inability to control attentional and cognitive processes is involved (obsessive-compulsive disorder (Swerdlow et al. 1993)), or where anxiety and exaggerated startle occur (posttraumatic stress disorder (Grillon et al. 1996)). The focus of schizophrenia research has been turning from studies of structural and functional brain abnormalities to an increasing emphasis on possible etiologic factors. Neurodevelopmental theories of schizophrenia postulate that the psychopathology of schizophrenia may derive from alterations of brain organization secondary to defective ontogenesis (Weinberger 1996;Raedler et al. 1998). A causal relationship pertaining to disturbed brain ontogenesis and schizophrenia comes from epidemiological studies that have identified several risk factors that, acting during pregnancy, increase the incidence of the disease in offspring. Maternal infection with influenza virus in the second trimester of preg...

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Section: Discussionsupporting

confidence: 83%

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

Borrell

Vela²,

Arévalo-Martı́n³

et al. 2002

Neuropsychopharmacology

280

191

View full text Add to dashboard Cite

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“…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-␥. 22 Interestingly, in our previous study, 13 we found that decreased IL-2 production may be associated with an increased IL-2 serum level in schizophrenic patients, supporting the T cell exhaustion theory that lower IL-2 production may be induced by a consequence of overproduction of in vivo IL-2.…”

Section: Introductionsupporting

confidence: 68%

“…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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“…Aberrations in interleukin 2 (IL-2) regulation, including elevated soluble IL-2 receptor in sera of Caucasian and Korean schizophrenic patients (Rapaport et al, 1994) and decreased IL-2 production after mitogen stimulation (Kim et al, 1998), have been regarded as indirect evidence that schizophrenia may have an infectious or autoimmune basis. That viruses (or autoimmunity stimulated by viruses) may be involved in the pathogenesis of major psychiatric disorders, such as schizophrenia, bipolar disorder and major depression (Kirch and Alexander, 1992), is a concept which is gaining increasing support.…”

mentioning

confidence: 99%

Failure to demonstrate Borna disease virus genome in peripheral blood mononuclear cells from psychiatric patients in Korea

Kim¹,

Kim²,

Choi³

et al. 1999

J Neurovirol

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Decreased Interleukin-2 Production in Korean Schizophrenic Patients

Cited by 60 publications

References 17 publications

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

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

Failure to demonstrate Borna disease virus genome in peripheral blood mononuclear cells from psychiatric patients in Korea

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