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Fortschr Neurol Psychiatr 2009; 77(6): 334-345
DOI: 10.1055/s-0028-1109420
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Die Bedeutung des TNF-α-Systems für Erkrankungen des Gehirns

The Relevance of the TNF-α System in Psychiatric DisordersH. Himmerich1, 2 , M. Berthold-Losleben1 , T. Pollmächer3
  • 1Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum der RWTH Aachen
  • 2Klinik und Poliklinik für Psychiatrie, Universitätsklinikum Leipzig
  • 3Zentrum für psychische Gesundheit, Klinikum Ingolstadt
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Publication History

Publication Date:
04 May 2009 (online)

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Zusammenfassung

Es gibt vielfache Hinweise in der Literatur darauf, dass Veränderungen des Immunsystems oder spezifischer ausgedrückt des Zytokinsystems, zu dem auch der Tumornekrosefaktor-alpha (TNF-α) zählt, an der Entstehung neurologischer Erkrankungen aus dem entzündlichen und neurodegenerativen Formenkreis wie der Multiplen Sklerose, dem Morbus Alzheimer und Morbus Parkinson sowie psychiatrischer Erkrankungen wie der Depression, Schizophrenie und Narkolepsie beteiligt sind. Zudem bestehen Zusammenhänge zwischen Zytokinkonzentrationen im Serum und dem Risiko zereobrovaskulärer Ereignisse. Auch Körpergewicht, Alter und neuroendokrinologische Mechanismen haben einen starken Einfluss auf die Plasmakonzentrationen von TNF-α und seiner löslichen Rezeptoren (sTNF-Rs). TNF-α könnte zur Pathogenese dieser Erkrankungen durch eine Aktivierung der Hypothalamus-Hypophysen-Nebennierenrinden-Achse (HPA-Achse), eine Aktivierung von Serotonintransportern, eine Stimulation der Indolamin-2,3-Dioxygenase, die zur Tryptophandepletion führt, einen immunologisch vermittelten Neuronenuntergang oder neurotoxische Effekte durch Glutamatausschüttung beitragen. Auch eine psychopharmakologische Therapie beeinflusst das Immunsystem. Bei der antipsychotischen Therapie ist möglicherweise ein Teil der Wirkung bestimmter Antipsychotika über eine Induktion inflammatorischer Zytokine vermittelt. Es ist zu wünschen, dass diese Überlegungen in naher Zukunft zu immunmodulatorischen Therapiestrategien für psychisch kranke Patienten führen.

Abstract

Changes regarding the immune system and specifically the cytokine system, of which tumor necrosis factor-alpha (TNF-α) is a part, have been shown to be involved in the development of neurological and psychiatric disorders such as multiple sclerosis, Parkinson‘s and Alzheimer‘s disease, depression, schizophrenia or narcolepsy. Besides, there is evidence that the risk of stroke correlates with the serum concentrations of different cytokines. Additionally, body weight, age and neuroendocrinological mechanism have a strong influence upon plasma levels of TNF-α and its soluble receptors (sTNF-Rs). TNF-α might contribute to the pathogenesis of these diseases by an activation of the hypothalamo-pituitary-adrenocortical (HPA) axis, an activation of neuronal serotonin transporters, the stimulation of the indoleamine 2,3-dioxygenase which leads to tryptophan depletion, by immunologically mediated destruction of neurons, or neurotoxic release of glutamate. Psychotropic drugs influence the TNF-α system, too. During psychopharmacological treatment of schizophrenia, some antipsychotics might act on neurotransmitter metabolism via inducing the proinflammatory cytokine system. Hopefully, these hypotheses may lead to new therapeutical strategies for psychiatric patients in the near future.

Schlüsselwörter

TNF-α - Depression - Schizophrenie - Narkolepsie - Psychopharmaka - Zytokin - Entzündung

Key words

TNF-α - depression - schizophrenia - narcolepsy - psychopharmacology - cytokine - inflammation

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Prof. Dr. med. Hubertus Himmerich

Klinik und Poliklinik für Psychiatrie, Universitätsklinikum Leipzig, AöR

Semmelweisstraße 10

04107 Leipzig

Email: Hubertus.Himmerich@medizin.uni-leipzig.de