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Neuroendokrin-immune Interaktionen bei rheumatischen Krankheiten

Neuroendocrine immune interactions in rheumatic diseases

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Zusammenfassung

Klinische Beobachtungen zeigten einen starken Einfluss des neuroendokrinen Systems auf das Immunsystem bei chronisch entzündlichen Erkrankungen: 1. Abschwächung der rheumatoiden Arthritis (RA) während der Schwangerschaft; 2. mehr Frauen als Männer haben eine Autoimmunkrankheit; 3. negativer Einfluss einer ovulationsfördernden Therapie, der Antikonzeptiva und der Hormonersatztherapie; 4. schützender Effekt der Hemiplegie; 5. Einfluss von psychischem Stress auf den Krankheitsverlauf und 6. Bedeutung zirkadianer Rhythmen auf das Krankheitsgeschehen.

Die Wirkung der verschiedenen Hormone und Neurotransmitter wird durch unterschiedliche Faktoren beeinflusst, durch: 1. den Immunstimulus (fremde Antigene oder Autoantigene) und die darauf folgenden antigenspezifischen Immunantworten; 2. die beteiligten Zellen während der verschiedenen Phasen der Krankheit; 3. das Zielorgan mit seiner spezifischen Mikroumgebung; 4. den Zeitpunkt der Hormon- bzw. Neurotransmitterwirkung in Beziehung zum Krankheitsverlauf; 5. die Konzentration von Hormonen und Neurotransmittern; 6. die Variabilität der Expression von Rezeptoren abhängig von der Mikroumgebung und dem Zelltyp und 7. die intrazelluläre und extrazelluläre Metabolisierung der Hormone bzw. Neurotransmitter (entscheidend für wichtige biologisch aktive Metabolite mit sehr unterschiedlichen antiinflammatorischen und proinflammatorischen Eigenschaften).

Der zirkadiane Rhythmus von krankheitsbedingten Symptomen mit einer Spitze in den frühen Morgenstunden bestätigt, dass das neuroendokrine System einen starken Einfluss auf diese chronischen Entzündungskrankheiten hat. Der Einfluss wird durch die zirkadiane Schwankung der Aktivität von hormonellen und neuronalen Achsen übertragen, welche das Gehirn und Entzündungszellen verbinden.

Diese Überlegungen können in Zukunft zu neuen Therapiestrategien bei Entzündungskrankheiten führen.

Abstract

Clinical observations in chronic inflammatory diseases have demonstrated the significant influence of neuroendocrine mechanisms on the immune system: (1) Amelioration of rheumatoid arthritis during pregnancy; (2) preponderance of women versus men with respect to autoimmune diseases; (3) negative effects of ovulation-inducing therapy, oral contraceptives, and hormone replacement therapy; (4) protective effect of hemiplegia; (5) influence of psychological stress on inflammation; and (6) influence of circadian rhythms on inflammatory symptoms.

The effects of different hormones and neurotransmitters on the immune system are influenced by: (1) the immune stimulus (foreign antigens or autoantigens) and subsequent antigen-specific immune responses, (2) the cell types involved during different phases of the disease, (3) the target organ with its specific microenvironment, (4) the timing of hormone or neurotransmitter increase in relation to the disease course, (5) the concentration of hormones and neurotransmitters, (6) the variability in expression of receptors depending on the microenvironment and the cell type, and (7) the intra- and extracellular peripheral metabolism of hormones and neurotransmitters leading to important biologically active metabolites with quite different anti- and proinflammatory functions.

The circadian rhythm of disease-related symptoms with a peak in the early morning hours confirms that the neuroendocrine system has a strong influence on these chronic immune/inflammatory diseases. The influence is transmitted by the circadian fluctuation in the activity of hormonal and neuronal pathways linking the brain to immune cell activation.

These considerations could lead to novel therapeutic strategies for rheumatic diseases in the future.

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Rainer H. Straub erhielt im Rahmen von Beratungsgesprächen Honorare von Firma Merck Serono und Nitec Pharma. Die Studien der Gruppe von Rainer H. Straub wurden von der DFG und dem BMBF unterstützt.

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  1. Klinik und Poliklinik für Innere Medizin I, Universitätsklinikum Regensburg, 93042 , Regensburg, Deutschland

    R.H. Straub & A. Fassold

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  2. A. Fassold
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Correspondence to R.H. Straub.

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Straub, R., Fassold, A. Neuroendokrin-immune Interaktionen bei rheumatischen Krankheiten. Z. Rheumatol. 69, 340–348 (2010). https://doi.org/10.1007/s00393-010-0637-x

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