Das Stresskonzept von Allostase und Allostatic Load: Einordnung psychoneuroimmunologischer Forschungsbefunde an Beispielen zur Autoimmunität und Onkologie

Zusammenfassung

Klassische Theorien definieren Stress als Reaktion auf eine Bedrohung der Homöostase eines Organismus, welche eine Anpassungsreaktion erfordert. Langfristige Konsequenzen in Bezug auf die Entwicklung von Erkrankungen zu postulieren ist auf der Grundlage solcher Konzepte jedoch problematisch. Das Konzept von Allostatic Load ermöglicht Aussagen über Reaktionssequenzen von Stressmediatoren und von diesen initiierten Effekten und pathogenen Folgen. Stressmediatoren werden kurzfristig und in geringen Konzentrationen adaptiv sezeniert, können aber langfristig zu schädigenden Effekten führen. Dieses Konzept erlaubt die Formulierung von Ursache-Wirkungs-Kaskaden, um den Zusammenhang einer Dysregulation von Stressmediatoren wie Glukokortikoiden und Katecholaminen und der Anfälligkeit für Erkrankungen zu beschreiben. In der vorliegenden Arbeit beschreiben wir zunächst den theoretischen Hintergrund des Konzeptes von Allostatic Load. Anschließend übertragen wir dieses Konzept auf Forschungsergebnisse, welche darauf hinweisen, dass eine Dysregulation der Stressreaktionssysteme bei multipler Sklerose und Brustkrebs für die Pathogenese oder die Krankheitsentwicklung bedeutsam sein könnte. Stressmediatoren und ihre Folgen in der Reaktionskaskade sind jedoch in einem nicht-linearen Netzwerk miteinander verbunden.

Abstract

Classical theories have conceptualized stress as a reaction to threat to the homeostasis within the organism requiring an adaptive response. However, postulating mechanisms that could link such responses to long-term detrimental health outcomes remains difficult. The allostatic load concept enables us to think about how mediators can be protective in the short run but may have damaging effects when overused and/or not shut off. It further facilitates the formulation of cause-effects cascades to explain the link of dysregulations in stress mediators such as glucocorticoids and catecholamines and increased susceptibility for certain diseases. In the first section, we briefly summarize the theoretical background. We then employ the concept to integrate findings from basic and clinical research on dysregulations of the stress response systems in multiple sclerosis and breast cancer. Based on this model, it seems likely that such dysregulations are implicated in progression and possibly pathogenesis of these diseases. When using allostatic load as a heuristic model, one needs to consider that stress mediators and outcomes are interconnected in a non-linear network.

Stress - psychoneuroimmunology - oncology - multiple sclerosis

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