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Dopamine mediates vagal modulation of the immune system by electroacupuncture

Nature Medicine volume 20, pages 291–295 (2014)Cite this article

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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 settings1,2,3. Neuronal networks represent physiological mechanisms, selected by evolution to control inflammation, that can be exploited for the treatment of inflammatory and infectious disorders3. 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 insufficiency4, 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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Figure 1: Electroacupuncture controls systemic inflammation in sepsis via the sciatic and vagus nerves and catecholamines from the adrenal glands.
Figure 2: Electroacupuncture induces the expression of DOPA decarboxylase and dopamine.
Figure 3: Electroacupuncture rescues mice from established polymicrobial peritonitis.
Figure 4: D1 receptor agonist rescues mice from established polymicrobial peritonitis with adrenal insufficiency.

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Acknowledgements

We thank P. Morcillo, J.M. Inclan-Rico and J.R. Berlin for their comments and suggestions and M. Marks (University of Colorado) and B. Kobilka (Stanford University) for the α7nAChR and β2AR knockout mice. R.T.-R. was supported by the University Autónoma Benito Juarez de Oaxaca. M.d.R.T.-B. was supported by the Mexican National Council for Science and Technology. L.U. is supported by the faculty program of the Department of Surgery of the New Jersey Medical School, the Foundation of University of Medicine and Dentistry of New Jersey and US National Institutes of Health grant RO1-GM084125.

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Authors and Affiliations

  1. Department of Surgery, Laboratory of Anti-inflammatory Signaling, Rutgers University New Jersey Medical School, Newark, New Jersey, USA

    Rafael Torres-Rosas, Ghassan Yehia, Geber Peña, Priya Mishra, Maria del Rocio Thompson-Bonilla & Luis Ulloa

  2. Medical Research Unit on Immunochemistry, National Medical Center Siglo XXI, Mexico City, Mexico

    Rafael Torres-Rosas, Lourdes Andrea Arriaga-Pizano & Armando Isibasi

  3. The Institute for Social Security and Services for the State's Employees Research Institute, Mexico City, Mexico

    Maria del Rocio Thompson-Bonilla

  4. Laboratory of Immunobiology, Hospital Juárez de México, Mexico City, Mexico

    Mario Adán Moreno-Eutimio

  5. Center of Immunology and Inflammation, Rutgers University New Jersey Medical School, Newark, New Jersey, USA

    Luis Ulloa

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Contributions

R.T.-R., G.Y., G.P., P.M. and M.d.R.T.-B. performed the experiments, prepared the figures and revised the article. M.A.M.-E., L.A.A.-P. and A.I. contributed to the design of the study and revised the paper. L.U. designed and directed the study and wrote the paper.

Corresponding author

Correspondence to Luis Ulloa.

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Torres-Rosas, R., Yehia, G., Peña, G. et al. Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat Med 20, 291–295 (2014). https://doi.org/10.1038/nm.3479

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