Elevated interleukin-6 in schizophrenia

Kammen, Daniël P. van; McAllister-Sistilli, Cathy G.; Kelley, Mary E.; Gurklis, John A.; Yao, Jeffrey

doi:10.1016/s0165-1781(99)00053-0

Cited by 74 publications

(37 citation statements)

References 45 publications

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“…The immune hypothesis of schizophrenia came from the observation that schizophrenic patients have been found to have some immune dysregulation and higher circulating levels of pro-inflammatory cytokines [Shintani et al, 1991;Ganguli et al, 1994;Naudin et al, 1996Naudin et al, , 1997Lin et al, 1998;Van Kammen et al, 1999]. Several studies have also reported that typical and atypical antipsychotics may have a negative immunomodulatory effect [Maes et al, 1995;Pollmacher et al, 1996;Muller et al, 1997].…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal levels of proinflammatory cytokines and their receptors have been found in peripheral blood and cerebrospinal fluid of schizophrenic patients, suggesting the presence of immune activation [Licinio et al, 1993;Maes et al, 1995;Monteleone et al, 1997;Naudin et al, 1997;Maes et al, 2000]. Immune abnormalities in schizophrenia have been confirmed in studies reporting increased circulating levels of proinflammatory cytokines such as TNF alpha, IL-6, IL-1 beta [Shintani et al, 1991;Ganguli et al, 1994;Naudin et al, 1996Naudin et al, , 1997Lin et al, 1998;Van Kammen et al, 1999]. Given that cytokines have been involved in the regulation of many neuronal functions such as neurotransmission, synaptic plasticity, and neuronal survival [Nawa et al, 2000] these molecules may represent the pathogenetic link between the immune, the neurotransmission, and the neurodevelopmental hypotheses of schizophrenia.…”

Section: Introductionmentioning

confidence: 95%

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MCP‐1 gene (SCYA2) and schizophrenia: A case‐control association study

Mundo

Altamura

Vismara

et al. 2004

American J of Med Genetics Pt B

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Dysregulation of the inflammatory response system has been linked to the pathophysiology of schizophrenia. Abnormal levels of proinflammatory cytokines and their receptors have been found in peripheral blood and cerebrospinal fluid of schizophrenic patients, suggesting the presence of immune activation. Monocyte chemoattractant protein 1 (MCP-1) influences the expression of cytokines related to T helper responses. MCP-1 also exerts several effects on monocytes, including the expression of several proinflammatory genes. The A-2518G polymorphism of the MCP-1 gene (SCYA2) appears to affect the transcriptional activity and monocyte MCP-1 production. The aim of this case-control study was to investigate the potential role of SCYA2 (A-2518G polymorphism) in conferring susceptibility to schizophrenia and to the resistance to antipsychotic treatment. The sample studied consisted of 191 DSM-IV schizophrenia or schizoaffective disorder (depressive subtype) patients and 161 matched healthy controls. No significant genotypic (chi(2) = 0.278, df = 2, P = 0.986) or allelic (chi(2) = 0.021, df = 1, P = 0.884) association was found between the A-2518G variant of the SCYA2 and the diagnosis. No differences in the age at onset of schizophrenia were found between the three genotype groups identified. Significant genotypic association was found between the A-2518G variant of the SCYA2 and the resistance to antipsychotic treatment (chi(2) = 6.26, df = 2, P = 0.04), with resistant patients more frequently carrying the G allele. The odds ratio associated to the presence of the G allele was 2.39 (95% CI = 1.14-4.98). These data suggest that the A-2518G variant of the SCYA2 has not a major role in the pathogenesis of schizophrenia, while it could be implicated in the resistance to antipsychotic treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

MCP‐1 gene (SCYA2) and schizophrenia: A case‐control association study

Mundo

Altamura

Vismara

et al. 2004

American J of Med Genetics Pt B

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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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“…Elevated plasma levels of IL-6 in patients with schizophrenia have been reported (Shintani et al 1991 ;Ganguli et al 1994 ;Maes et al 1995 ;Lin et al 1998 ;van Kammen et al 1999 ). It seems that the increased production of NO in the brain of patients with schizophrenia can occur involving induction of IL-6.…”

Section: The Adma Nos Inhibition and Regulation Of Nitric Oxide Genmentioning

confidence: 99%