March 10, 2014

Electroacupuncture Reduces Sepsis in Mice

Acupuncture needles.

Researchers found that electroacupuncture in mice reduced the inflammation responsible for sepsis. The mechanisms underlying the therapy hint at new approaches to treat inflammatory disorders.

Sepsis occurs when the body’s immune system goes into overdrive to fight an infection. Infection-fighting chemicals released into the blood can sometimes trigger widespread, damaging inflammation. This can rapidly lead to blood clots and failure of multiple organs, including the lungs, kidney, and liver.

Sepsis is a leading cause of death in hospital intensive care units and accounts for about 9% of overall deaths in the U.S. People who survive may have permanent organ damage, cognitive impairment, and physical disability. Although antibiotics may be given to treat the infection, they do not control the resulting inflammation. There’s no treatment currently approved by the U.S. Food and Drug Administration for severe sepsis.

Inflammation is known to be modulated by the vagus nerve. Unfortunately, it’s difficult to directly stimulate this nerve without anesthetics and surgery. A team of researchers, led by Dr. Luis Ulloa of Rutgers University, set out to determine whether they could use eletroacupuncture to activate this nerve and thus modify inflammatory responses. The research was supported in part by NIH’s National Institute of General Medical Sciences (NIGMS). Results appeared in the March 2014 issue of Nature Medicine.

Acupuncture involves stimulation of specific points on the body, known as acupoints. It’s often performed by manipulating thin metallic needles inserted through the skin. In electroacupuncture, the inserted needles are electrically stimulated.

The researchers gave mice a bacterial infection and then performed electroacupuncture by inserting needle electrodes at a specific point near the knee. The treatment activated the sciatic nerve, which led to stimulation of the vagus nerve. Blood levels of several inflammatory markers were lowered. This effect was not seen when a wooden toothpick was inserted instead of the electrodes, or when a non-acupoint area was stimulated.

The electroacupuncture no longer reduced inflammation when the vagus nerve was cut. This nerve is known to inhibit the spleen’s production of inflammatory chemicals. Removal of the spleen in the mice, however, didn’t have an effect, indicating that the vagus nerve influenced inflammation through a novel route that didn’t involve the spleen.    

Further experiments showed that stimulation of the vagus nerve triggered the adrenal glands to release catecholamines, including dopamine and norepinephrine. The electroacupuncture activated an enzyme involved in the production of dopamine in the adrenal glands. Dopamine, in turn, inhibited production of inflammatory chemicals.

The team found that electroacupuncture wasn’t effective in treating mice whose adrenal glands were removed. Unfortunately, many patients with sepsis have problems with their adrenal glands, so electroacupuncture likely wouldn’t help them. To address this issue, the team focused in on dopamine. Dopamine has broad effects, activating many receptors, so they tested compounds that target specific receptors. Fenoldopam, which specifically activates dopaminergic receptor type 1, controlled inflammation and improved survival in experimental mouse models of adrenal insufficiency.

“Sepsis is the major cause of death in the hospital,” Ulloa says. “In many cases patients don’t die because of the infection. They die because of the inflammatory disorder they develop after the infection. Electroacupuncture and specific therapeutics that mimic dopamine are complementary strategies for the treatment of sepsis.”

—by Carol Torgan, Ph.D.

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References: Dopamine mediates vagal modulation of the immune system by electroacupuncture. Torres-Rosas R, Yehia G, Peña G, Mishra P, Del Rocio Thompson-Bonilla M, Moreno-Eutimio MA, Arriaga-Pizano LA, Isibasi A, Ulloa L. Nat Med. 2014 Mar;20(3):291-5. doi: 10.1038/nm.3479. Epub 2014 Feb 23. PMID: 24562381.

Funding: NIH’s National Institute of General Medical Sciences (NIGMS); University Autónoma Benito Juarez de Oaxaca, Mexican National Council for Science and Technology, Department of Surgery of the New Jersey Medical School, and the Foundation of University of Medicine and Dentistry of New Jersey.