Elevated circulating levels of IL-6 in schizophrenia

Naudin, Jean; Mège, Jean Louis; Azorin, Jean‐Michel; Dassa, D.

doi:10.1016/0920-9964(96)00014-x

Cited by 104 publications

(52 citation statements)

References 21 publications

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“…Previous reports have found an association with IL-6 and acute symptomatology in BD 20 and SZ. 32 Considering that our comparison involved patients in non-acute phases of illness (euthymic BD vs. chronic SZ), our finding that there is an increased presence of IL-6 in SZ provides further evidence of a chronic immune activation and inflammatory syndrome in SZ. 23 While increased IL-6 seems to be state-dependent in BD, it seems to be a trait in patients with SZ.…”

Section: Discussionmentioning

confidence: 75%

Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance

Kunz¹,

Ceresér²,

Goi³

et al. 2011

Rev. Bras. Psiquiatr.

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Objective: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders. Method: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-α, IL-6, and IL-10 were examined by sandwich ELISA. Results: IL-6 levels were increased in schizophrenia patients when compared to controls (p < 0.0001) and euthymic bipolar disorder patients (p < 0.0001). IL-6 levels were no different in controls compared to euthymic bipolar disorder patients (p = 0.357). IL-10 was lower in controls compared to schizophrenia patients (p = 0.001) or to bipolar disorder patients (p = 0.004). There was no significant difference in TNF-α serum levels among the groups (p = 0.284). Gender-based classification did not significantly alter these findings, and no correlation was found between the antipsychotic dose administered and cytokine levels in patients with schizophrenia. Discussion: These findings evidence a chronic immune activation in schizophrenia. Bipolar disorder seems to present an episode-related inflammatory syndrome. Increased anti-inflammatory factor IL-10 in bipolar disorder and schizophrenia suggests different patterns of inflammatory balance between these two disorders. Results further support the need to investigate cytokines as possible biomarkers of disease activity or treatment response.Descriptors: Bipolar disorder; Schizophrenia; Interleukin-6; Interleukin-10; Tumor necrosis factor-alpha (p = 0,284 Resumo Objetivo: Pesquisas sugerem as citocinas como potenciais mediadores da interação entre os sistemas imune e neuroendócrino, e que existe um estado pró-inflamatório associado com transtorno bipolar e esquizofrenia. O objetivo deste estudo é comparar os níveis de citocinas entre os dois distúrbios. Método: Vinte pacientes com transtorno bipolar eutímicos, 53 pacientes com esquizofrenia crônica estabilizados e 80 controles saudáveis foram recrutados. Todos os indivíduos eram não-fumantes e não-obesos. As citocinas TNF-α, IL-6 e IL-10 foram examinadas por ELISA sanduíche. Resultados: A IL-6 estava aumentada nos pacientes com esquizofrenia quando comparados aos controles (p < 0,0001) e aos pacientes bipolares eutímicos (p < 0,0001). Os níveis de IL-6 não foram diferentes nos controles em comparação com pacientes com transtorno bipolar eutímicos (p = 0,357). Os níveis de IL-10 foram menores nos controles quando comparados aos pacientes com esquizofrenia (p = 0,001) ou aos bipolares (p = 0,004). Não houve diferença significativa nos níveis séricos de TNF-α entre os grupos

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Section: Discussionmentioning

confidence: 75%

Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance

Kunz¹,

Ceresér²,

Goi³

et al. 2011

Rev. Bras. Psiquiatr.

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“…In particular, elevated plasma levels of IL-6 have been consistently reported in patients and first-degree relatives with mood disorders (Ganguli et al, 1994;Naudin et al, 1996;Nunes et al, 2005), and correlate with exacerbation of psychotic episodes (Ganguli et al, 1994;Naudin et al, 1996;Lin et al, 1998;Zhang et al, 2002;Kudoh et al, 2003;Nunes et al, 2005). Furthermore, treatment with atypical antipsychotics can alter circulating cytokines (Pollmacher et al, 2000).…”

Section: Mechanism Of Activation Of Nox2 In Neuronsmentioning

confidence: 99%

Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?

2009

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An imbalance in the redox-state of the brain may be part of the underlying pathophysiology in schizophrenia. Inflammatory mediators, such as IL-6, which can tip the redox balance into a prooxidant state, have been consistently found to be altered in schizophrenia patients. However, the relationship of altered redox-state to altered brain functions observed in the disease has been unclear. Recent data from a pharmacological model of schizophrenia suggest that redox and inflammatory imbalances may be directly linked to the pathophysiology of the disease by alterations in fast-spiking interneurons. Repetitive adult-exposure to the NMDA-R antagonist ketamine increases the levels of the proinflammatory cytokine interleukin-6 in brain which, through activation of the superoxide-producing enzyme NADPH-oxidase (Nox2), leads to the loss of the GABAergic phenotype of PV-interneurons and to decreased inhibitory activity in prefrontal cortex. This effect is not observed after a single exposure to ketamine, suggesting that the first exposure to the NMDA-R antagonist primes the brain such that deleterious effects on PVinterneurons appear upon repetitive exposures. The effects of activation of the IL-6/Nox2 pathway on the PV-interneuronal system are reversible in the adult brain, but permanent in the developing cortex. The slow development of PV-interneurons, while essential for shaping of neuronal circuits during postnatal brain development, increases their vulnerability to deleterious insults that can permanently affect their maturational process. Thus, in individuals with genetic predisposition, the persistent activation of the IL-6/Nox2 pathway may be an environmental factor that tips the redoxbalance leading to schizophrenia symptoms in late adolescence and early adulthood.

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“…Various studies have analyzed serum and plasma levels of cytokines, including interleukin-2 (IL-2) (Cazzullo et al, 2002(Cazzullo et al, , 2001Kim et al, 2001;Szulc et al, 2001;Theodoropoulou et al, 2001), IL-4 (Cazzullo et al, 2002(Cazzullo et al, , 2001), IL-6, (Kim et al, 2001;Kudoh et al, 2001;Haack et al, 1999;Akiyama, 1999;Monteleone et al, 1997), IL-10 (Cazzullo et al, 2002Maes et al, 2002), and TNF-a (Theodoropoulou et al, 2001;Kudoh et al, 2001;Haack et al, 1999;Monteleone et al, 1997;Naudin et al, 1996), in order to better understand the role of immune activation in schizophrenic disorders (Muller et al, 2001). The findings from such studies in the periphery have been contradictory.…”

Section: Studies Of Immune Activation In Schizophreniamentioning

confidence: 99%

Elevated Interleukin-6 in the Cerebrospinal Fluid of a Previously Delineated Schizophrenia Subtype

Garver

Tamas

Holcomb

2003

Neuropsychopharmacol

133

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Evidence of immune activation has occasionally, but not consistently, been reported in schizophrenia. Investigations of cytokine abnormalities in serum, and occasionally in CSF, have yielded inconsistent results, which have been difficult to resolve. In such studies, schizophrenia has been assumed to consist of a single process rather than a group of disorders. This study assesses differences in the proinflammatory cytokine, interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) in two previously delineated subtypes of schizophrenics ('delayed-responders' (DR) (n ¼ 23) and 'poor-responders' (PR) (n ¼ 8)) during periods of neuroleptic-free psychotic exacerbation, and in a comparison group of normal controls (n ¼ 14). The two response subtypes were separated by subsequent treatment response (greater/less than 60% reduction of SAPS scores from baseline during 6 months of systematic treatment). The IL-6 assay, a sandwich enzyme-linked immunosorbent assay, was sensitive and reliable to detect IL-6 levels in the CSF of all subjects. CSF IL-6 was found to be significantly higher in the DR than the PR (P ¼ 0.017) and the controls (P ¼ 0.013). In addition to supporting the concept of heterogeneity in schizophrenia, this study also provides evidence that a central immune process may be occurring centrally in one subtype of schizophrenia.

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Elevated circulating levels of IL-6 in schizophrenia

Cited by 104 publications

References 21 publications

Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance

Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance

Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?

Elevated Interleukin-6 in the Cerebrospinal Fluid of a Previously Delineated Schizophrenia Subtype

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Elevated circulating levels of IL-6 in schizophrenia

Cited by 104 publications

References 21 publications

Serum levels of IL-6, IL-10 and TNF-&#945; in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance

Serum levels of IL-6, IL-10 and TNF-&#945; in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance

Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?

Elevated Interleukin-6 in the Cerebrospinal Fluid of a Previously Delineated Schizophrenia Subtype

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Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance

Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance