title: Dopamine mediates vagal modulation of the immune system by electroacupuncture.
abstract: 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.
authors.affiliation: 1] Laboratory of Anti-inflammatory Signaling, Department of Surgery, Rutgers University New Jersey Medical School, Newark, New Jersey, USA. [2] Medical Research Unit on Immunochemistry, National Medical Center Siglo XXI, Mexico City, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Torres-Rosas
authors.affiliation: Laboratory of Anti-inflammatory Signaling, Department of Surgery, Rutgers University New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Yehia
authors.affiliation: Laboratory of Anti-inflammatory Signaling, Department of Surgery, Rutgers University New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Geber
authors.initials: G
authors.lastname: Peña
authors.affiliation: Laboratory of Anti-inflammatory Signaling, Department of Surgery, Rutgers University New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Mishra
authors.affiliation: 1] Laboratory of Anti-inflammatory Signaling, Department of Surgery, Rutgers University New Jersey Medical School, Newark, New Jersey, USA. [2] The Institute for Social Security and Services for the State's Employees Research Institute, Mexico City, Mexico.
authors.forename: Maria
authors.initials: M
authors.lastname: del Rocio Thompson-Bonilla
authors.affiliation: Laboratory of Immunobiology, Hospital Juárez de México, Mexico City, Mexico.
authors.forename: Mario Adán
authors.initials: MA
authors.lastname: Moreno-Eutimio
authors.affiliation: Medical Research Unit on Immunochemistry, National Medical Center Siglo XXI, Mexico City, Mexico.
authors.forename: Lourdes Andrea
authors.initials: LA
authors.lastname: Arriaga-Pizano
authors.affiliation: Medical Research Unit on Immunochemistry, National Medical Center Siglo XXI, Mexico City, Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Isibasi
authors.affiliation: 1] Laboratory of Anti-inflammatory Signaling, Department of Surgery, Rutgers University New Jersey Medical School, Newark, New Jersey, USA. [2] Center of Immunology and Inflammation, Rutgers University New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Ulloa
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015671:Electroacupuncture / Q000379:methods*; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D010538:Peritonitis / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D012584:Sciatic Nerve / Q000473:pathology; D018805:Sepsis / Q000276:immunology / Q000628:therapy*; D014630:Vagus Nerve / Q000276:immunology*
chemical_list: D002395:Catecholamines; D016207:Cytokines; D008070:Lipopolysaccharides; D017447:Receptors, Dopamine D1; D004296:Dopa Decarboxylase; D004298:Dopamine