I’ve seen actual biochemical evidence at a talk at the university that a good chunk of the cardiovactular benefit of exercise might come not from the metabolic effects but from it changing one’s mood and this then feeding into changes in the inflammatory pathway.
How does the biochemistry of mood changes feeding into the inflammatory pathway work?
A lot of the interaction between the nervous system and immune system is just suspected without being understood. Some is being figured out however.
A few years ago I had the good fortune to see a talk by Dr. Kevin Tracey, a guy who has done a lot of work on modulation of the immune system via drugs. In it he laid out the history behind his discovery of what he calls the inflammatory reflex, a neurological circuit that modulates the ability of circulating immune system cells to produce TNF and other molecules involved in inflammation.
The short version of what he showed us is that he found a branch of the vagus nerve enervates an enteric ganglion in your abdomen which then sends a norepinephrine-secreting nerve fiber into your spleen. In your spleen, the nerve fibers branch out and form what look for all the world like synapses with a weird population of immobilized lymphocytes. These look like lymphocytes except that they are expressing genes that act as norepinephrine receptors and the production pathway for another neurotransmitter, acetylcholine. When this nerve arc is activated these cells produce acetylcholine and the macrophages and other circulating immune system cells which are temporarily hung up during their passage through your spleen receive the signal and become much less prone to be activated into producing inflammatory signaling molecules for something like a day, I don’t remember the exact timeframe. Incidentally, inflammatory signals in peripheral tissues being suppressed by acetylcholine is also partially why most smokers won’t get inflammatory bowel disease – nicotine is a mimic of acetylcholine (which blasts all your receptors hard rather than just those at the ends of particular fibers hence all the myriad psychological and physiological effects). It’s more complicated than that (of course it is, its biology) and it appears that there are particular circumstances in which nicotine can drive inflammation too, but overall thats its net effect.
Your vagus nerve is a key part of your parasympathetic autonomic nervous system, known for being responsible for lowering heart rate and regulating digestion when you are at rest and affecting a bunch of hormone glands. It regulates things like heart rate and blood pressure and digestion rate and hormone production with levels of arousal and mood. Its activity is strongly affected by mood and wakefulness and can be modulated to a point by all those lovely meditative/biofeedback etc things that some people do.
Dr. Tracy found that patients with autoimmune diseases tended to have quieter than average vagus nerve activity and that by cutting or overstimulating this particular vagus branch he could slow or accelerate the progression of genetically predetermined arthritis in mice by a factor of two. He indicated that he suspects there are other such points of contact that haven’t been pinned down yet, such as there apparently being receptors for inflammatory cytokines somewhere in the brain itself that directly affect brain activity within seconds of sensing them, and the fact that mice which received a local anti-inflammatory drug treatment to the brain were much less prone to death from the immune overreactions of sepsis. Your enteric nervous system in particular is an interesting place where there’s lots of nerves in close proximity to lots of immune system cells and you might suspect there could be more crosstalk.
He speculated that the strong vagus activity that you get from cooldown from exercise after working your autonomic nervous system through its dynamic range might have something to do with reducing the inflammatory response that is partially responsible for atherosclerosis, as might the mood improvements that almost always come from going from no exercise to more exercise.
I actually read the more technical one when it came out in 2012. Basically took from it that there is a lot of research going on and a lot of crosstalk going on.
The bit about the movement of different muscles altering the permeability of different parts of the spinal cord to immune cell invasion was particularly weird.
How does the biochemistry of mood changes feeding into the inflammatory pathway work?
A lot of the interaction between the nervous system and immune system is just suspected without being understood. Some is being figured out however.
A few years ago I had the good fortune to see a talk by Dr. Kevin Tracey, a guy who has done a lot of work on modulation of the immune system via drugs. In it he laid out the history behind his discovery of what he calls the inflammatory reflex, a neurological circuit that modulates the ability of circulating immune system cells to produce TNF and other molecules involved in inflammation.
The short version of what he showed us is that he found a branch of the vagus nerve enervates an enteric ganglion in your abdomen which then sends a norepinephrine-secreting nerve fiber into your spleen. In your spleen, the nerve fibers branch out and form what look for all the world like synapses with a weird population of immobilized lymphocytes. These look like lymphocytes except that they are expressing genes that act as norepinephrine receptors and the production pathway for another neurotransmitter, acetylcholine. When this nerve arc is activated these cells produce acetylcholine and the macrophages and other circulating immune system cells which are temporarily hung up during their passage through your spleen receive the signal and become much less prone to be activated into producing inflammatory signaling molecules for something like a day, I don’t remember the exact timeframe. Incidentally, inflammatory signals in peripheral tissues being suppressed by acetylcholine is also partially why most smokers won’t get inflammatory bowel disease – nicotine is a mimic of acetylcholine (which blasts all your receptors hard rather than just those at the ends of particular fibers hence all the myriad psychological and physiological effects). It’s more complicated than that (of course it is, its biology) and it appears that there are particular circumstances in which nicotine can drive inflammation too, but overall thats its net effect.
Your vagus nerve is a key part of your parasympathetic autonomic nervous system, known for being responsible for lowering heart rate and regulating digestion when you are at rest and affecting a bunch of hormone glands. It regulates things like heart rate and blood pressure and digestion rate and hormone production with levels of arousal and mood. Its activity is strongly affected by mood and wakefulness and can be modulated to a point by all those lovely meditative/biofeedback etc things that some people do.
Dr. Tracy found that patients with autoimmune diseases tended to have quieter than average vagus nerve activity and that by cutting or overstimulating this particular vagus branch he could slow or accelerate the progression of genetically predetermined arthritis in mice by a factor of two. He indicated that he suspects there are other such points of contact that haven’t been pinned down yet, such as there apparently being receptors for inflammatory cytokines somewhere in the brain itself that directly affect brain activity within seconds of sensing them, and the fact that mice which received a local anti-inflammatory drug treatment to the brain were much less prone to death from the immune overreactions of sepsis. Your enteric nervous system in particular is an interesting place where there’s lots of nerves in close proximity to lots of immune system cells and you might suspect there could be more crosstalk.
He speculated that the strong vagus activity that you get from cooldown from exercise after working your autonomic nervous system through its dynamic range might have something to do with reducing the inflammatory response that is partially responsible for atherosclerosis, as might the mood improvements that almost always come from going from no exercise to more exercise.
Very interesting.
A couple of followup links: more popular and more technical.
I actually read the more technical one when it came out in 2012. Basically took from it that there is a lot of research going on and a lot of crosstalk going on.
The bit about the movement of different muscles altering the permeability of different parts of the spinal cord to immune cell invasion was particularly weird.