Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia - significance for activation of the kynurenine pathway.

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Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia - significance for activation of the kynurenine pathway.

Schwieler, Lilly (författare): Karolinska Institutet,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Larsson, Markus K (författare): Karolinska Institutet,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Skogh, Elisabeth (författare): Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Hälsouniversitetet,Region Östergötland, Psykiatriska kliniken

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Kegel, Magdalena E (författare): Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Orhan, Funda (författare): Karolinska Institutet,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Abdelmoaty, Sally (författare): Karolinska Institutet,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Finn, Anja (författare): Karolinska Institutet,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Bhat, Maria (författare): AstraZeneca, Research & Development, Innovative Medicines, Personalised Healthcare & Biomarkers, Science for Life Laboratory, Solna, Sweden / Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

Samuelsson, Martin (författare): Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Psykiatriska kliniken

Lundberg, Kristina (författare): Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten

Dahl, Marja-Liisa (författare): Karolinska Institutet,Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

Sellgren, Carl (författare): Karolinska Institutet,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Schuppe-Koistinen, Ina (författare): Karolinska Institutet,AstraZeneca, Research & Development, Innovative Medicines, Personalised Healthcare & Biomarkers, Science for Life Laboratory, Solna, Sweden / Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

Svensson, Camilla (författare): Karolinska Institutet,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Erhardt, Sophie (författare): Karolinska Institutet,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Engberg, Göran (författare): Karolinska Institutet,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

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2015-03-01
2015
Engelska.
Ingår i: Journal of Psychiatry & Neuroscience. - : CMA-CANADIAN MEDICAL ASSOC. - 1180-4882 .- 1488-2434. ; 40:2, s. 126-13

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BACKGROUND: Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway.METHODS: We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry.RESULTS: We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA.LIMITATIONS: The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age.CONCLUSION: We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-D-aspartate receptor antagonist KYNA in patients with schizophrenia.

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Av författaren/redakt...: Schwieler, Lilly; Larsson, Markus ...; Skogh, Elisabeth; Kegel, Magdalena ...; Orhan, Funda; Abdelmoaty, Sall ...; visa fler...; Finn, Anja; Bhat, Maria; Samuelsson, Mart ...; Lundberg, Kristi ...; Dahl, Marja-Liis ...; Sellgren, Carl; Schuppe-Koistine ...; Svensson, Camill ...; Erhardt, Sophie; Engberg, Göran; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

Artiklar i publikationen: Journal of Psych ...

Av lärosätet: Linköpings universitet; Karolinska Institutet

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Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia - significance for activation of the kynurenine pathway.

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