Dopamine Mediates Vagal Modulation
of the Immune
System by Electroacupuncture
Summary: Previous anti-inflammatory strategies against sepsis, a
leading cause of death in hospitals, had limited efficacy in clinical trials,
in part because they targeted single cytokines and the experimental models
failed to mimic clinical settings. Neuronal networks represent physiological
mechanisms, selected by evolution to control inflammation, that can be
exploited for the treatment of inflammatory and infectious disorders. Here, we
report that sciatic nerve activation with electroacupuncture controls systemic
inflammation and rescues mice from polymicrobial peritonitis.
Electroacupuncture at the sciatic nerve controls systemic inflammation by
inducing vagal activation of aromatic L-amino acid
decarboxylase, leading to the production of dopamine in the adrenal medulla.
Experimental models with adrenolectomized mice mimic clinical adrenal
insufficiency, increase the susceptibility to sepsis and prevent the anti-inflammatory
effects of electroacupuncture. Dopamine inhibits cytokine production via
dopamine type 1 (D1) receptors. D1 receptor agonists suppress systemic
inflammation and rescue mice with adrenal insufficiency from polymicrobial
peritonitis. Our results suggest a new anti-inflammatory mechanism mediated by
the sciatic and vagus nerves that modulates the production of catecholamines in
the adrenal glands. From a pharmacological perspective, the effects of
selective dopamine agonists mimic the anti-inflammatory effects of
electroacupuncture and can provide therapeutic advantages to control
inflammation in infectious and inflammatory disorders.
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