Researchers at Harvard Medical School successfully used acupuncture to tame cytokine storm in mice with systemic inflammation. In the study, published today in Neuron, acupuncture activated different signaling pathways that triggered either a pro-inflammatory or an anti-inflammatory response in animals with bacterially induced systemic inflammation.
Further, the team found that three factors determined how acupuncture affected response—site, intensity, and timing of treatment. Where in the body the stimulation occurred, how strong it was and when the stimulation was administered yielded dramatically different effects on inflammatory markers and survival.
"Our findings represent an important step in ongoing efforts not only to understand the neuroanatomy of acupuncture but to identify ways to incorporate it into the treatment arsenal of inflammatory diseases, including sepsis," said study principal investigator Qiufu Ma.
In the study, the team used electroacupuncture, which uses very thin electrodes inserted into the skin and into the connective tissue, offering better control of stimulation intensities than the traditional manual approach. Building on previous research pointing to neurotransmitters' role in inflammation regulation, the researchers focused on two specific cell types known to secrete them—chromaffin cells and noradrenergic neurons.
The team wanted to determine the precise role these nerve cells play in the inflammatory response. To do so, they used a novel genetic tool to ablate chromaffin cells or noradrenergic neurons. This allowed them to compare the response to inflammation in mice with and without these cells to determine just whether and how they were involved in modulating inflammation. The markedly different response in mice with and without such cells conclusively pinpointed these nerve cells as key regulators of inflammation.
In one set of experiments, researchers applied low-intensity electroacupuncture to a specific point on the hind legs of mice with cytokine storm caused by a bacterial toxin. This stimulation activated the vagus-adrenal axis, inducing secretion of dopamine from the chromaffin cells of the adrenal glands. Animals treated this way had lower levels of three key types of inflammation-inducing cytokines and had greater survival than control mice.
In another experiment, the team delivered high-intensity electroacupuncture to the same hindleg acupoint as well as to an acupoint on the abdomen of mice with sepsis. That stimulation activated noradrenergic nerve fibers in the spleen. The timing of treatment was critical, the researchers observed. High-intensity stimulation of the abdomen produced markedly different outcomes depending on when treatment occurred.
Animals treated with acupuncture immediately before they developed cytokine storm, experienced lower levels of inflammation during subsequent disease and fared better. This preventive measure of high-intensity stimulation increased survival from 20 to 80 percent. By contrast, animals that received acupuncture after disease onset and during the peak of cytokine storm experienced worse inflammation and more severe disease.