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Vagus Nerve Controls Intestinal Inflammation

From Cooling Inflammation

Macrophages release inflammatory signals (TNF, IL-1, IL-6, IL-18) that result in tissue inflammation. Nicotine is anti-inflammatory by acting on the acetylcholine receptors normally responsive to acetylcholine released by the vagus nerve. Acupuncture is anti-inflammatory by stimulating the vagus nerve-mediated effects on macrophages.

The relationship between the nervous and immune systems has been accepted as a reality, but has been elusive. Numerous examples in alternative medicine appear to show that a variety of treatments have immunological impacts, but explanations based on cellular biology have been slow to materialize. Here I will discuss some of the recent experiments that reveal obvious connections between nerves and macrophages that may explain in medical terms at least part of the efficacy of acupuncture.

Dilation of blood vessels that causes reddening, swelling and warmth of tissue inflammation results from changes at the cellular level. If the sentinel cells of a tissue, macrophages, are exposed to a bacterium, for example, receptors on the surface of the macrophages bind fragments of the bacterial cell wall, i.e. lipopolysaccharide (LPS) or endotoxin, and signal the expression of five dozen genes. Among these genes are inflammatory mediators, TNF, IL-1, IL-6, IL-18, that are released from the macrophages and trigger behavioral changes in the surrounding cells of the tissue, which are observed as inflammation.

Expression of the inflammatory genes is controlled by a master transcription factor, NFkB. Thus, LPS will signal a macrophage, NFkB is activated, inflammatory genes are expressed, mediators are secreted and tissue inflammation is observed. Dozens of different inputs determine if NFkB will be activated or quieted. Nicotine for example has been observed to block inflammation by LPS.

It has been shown that macrophages also have receptors for the neurotransmitter acetylcholine that is released by branches of the vagus nerve in the intestines. It has also been recently shown that excitation of the vagus nerve releases acetylcholine and blocks the response of intestinal macrophages to LPS. Thus, vagus stimulation is anti-inflammatory and blocks NFkB activation through a competing transcription factor, STAT3. Nicotine acts by binding to the acetylcholine receptors of the macrophages and is similarly anti-inflammatory.

Acupuncture appears to work by needle stimulation of the vagus nerve that sends signals to the brain. Returning nerve impulses via the vagus nerve subsequently release acetylcholine back into the surrounding tissue and block inflammation. In this context, acupuncture would be exploiting an existing inflammation dampening system, that would serve to localize spreading inflammatory signaling and emphasize the source of inflammation for action by the circulating elements of the immune system.

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