Sepsis – Die Bedeutung der neuroendokrinen Achse in der Pathophysiologie der Sepsis

Zusammenfassung

Immunsystem und ZNS können sich gegenseitig beeinflussen. Proinflammatorische Zytokine induzieren die Expression von Corticotropin-Releasing-Hormon (CRH) oder Arginin-Vasopressin (AVP) im Hypothalamus und adrenocorticotropem Hormon (ACTH) in der Hypophyse. Die hierdurch verursachte gesteigerte Kortisolfreisetzung entfaltet seine antiinflammatorische Wirkung durch Suppression der NF-κB-Aktivierung und durch Aktivierung antiinflammatorischer Zytokine.

Der cholinerg antiinflammatorische Pathway als efferenter Teil des inflammatorischen Reflexes ist ein weiterer Mechanismus neuronaler Inflammationskontrolle. Er besteht aus dem efferenten Anteil des N. vagus, dem Neurotransmitter Azetylcholin und der α7-Subunit des nikotinergen Azetylcholin-Rezeptors. Im Plexus coeliacus erfolgt wahrscheinlich die Weitergabe der Information an postsynaptische sympathische Fasern, die zur Milz ziehen und dort auf Zellen des Immunsystems einwirken. Cholinesterase-Inhibitoren führen in der experimentellen Sepsis zu antiinflammatorischen Effekten, wenn sie frühzeitig verabreicht werden.

Abstract

The immune system and the central nervous system are able to affect each other. Proinflammatory cytokines induce the expression of CRH or AVP in the hypothalamus and ACTH in the pituitary gland. Thus, enhanced adrenal release of cortisol suppresses the activation of NF-κB and activates antiinflammatory cytokines.

The cholinergic antiinflammatory pathway, the efferent arm of the inflammatory reflex, is another mechanism of the CNS to control inflammation. It consists of the efferent vagus nerve, the neurotransmitter actylcholine and the α7 subunit of the nicotinic acteylcholine receptor. Probably, the transmission of information takes place to postsynaptic sympathetic fibres in the celiac plexus which terminate in the spleen and act on splenic immune cells. Cholinesterase inhibitors have antiinflammatory effects in experimental sepsis when administered early.

Schlüsselwörter:

Sepsis - inflammatorischer Reflex - Cholinesterase-Inhibitoren - neuroendokrinen Achse

Keywords:

Sepsis - inflammatory reflex - cholinesterase inhibitors - neuroendocrine axis

Kernaussagen

• Immunsystem und ZNS können miteinander kommunizieren, sich gegenseitig beeinflussen und spezifische Reaktionen hervorrufen.

• Das sympathische Nervensystem kann durch proinflammatorische Zytokine aktiviert werden und efferent durch freigesetzte Katecholamine sowohl pro- als auch antiinflammatorisch wirken, je nach Rezeptorausstattung der Zielzelle.

• Proinflammatorische Zytokine induzieren die Expression von

  • Corticotropin-Releasing-Hormon (CRH) oder Arginin-Vasopressin (AVP) im Hypothalamus und

  • adrenocorticotropem Hormon (ACTH) in der Hypophyse.

• Die durch ACTH verursachte gesteigerte Kortisol-Freisetzung entfaltet seine antiinflammatorische Wirkung durch Suppression der NF-κB-Aktivierung und durch Aktivierung der Synthese von IL-4 und IL-10.

• Der cholinerg antiinflammatorische Pathway als efferenter Teil des inflammatorischen Reflexes ist ein Mechanismus der neuronalen Inflammationskontrolle.

• Der cholinerg antiinflammatorische Pathway besteht aus dem efferenten Anteil des N. vagus, dem Neurotransmitter Azetylcholin und der α7-Subunit des nikotinergen Azetylcholin-Rezeptors.

• Im Plexus coeliacus erfolgt wahrscheinlich die Weitergabe der Information an postsynaptische sympathische Fasern, die zur Milz ziehen.

• Cholinesterase-Inhibitoren führen in der experimentellen Sepsis zu antiinflammatorischen Effekten, wenn sie frühzeitig verabreicht werden.

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