Tuesday, June 18, 2013

Immune Function

SNS as Interface Between Brain and Immune System

In 2000, a team of U.S Government scientists at the National Institutes of Health released a treatise entitled "The Sympathetic Nerve - An Integrative Interface between Two Supersystems: The Brain and the Immune System." They began by pointing out that all of the immune organs have rich sympathetic innervation. "Lymphoid organs, similar to blood vessels, receive predominantly sympathetic/noradrenergic and sympathetic/neuropeptide Y (NPY) innervation." (Elenkov et al. 2000; see also Madden et al., 1995).

Elenkov points out numerous effects that NE is known to have on immune function, and spends a good deal of time trying to distinguish between effects produced by NE in the blood and NE delivered by sympathetic nerve terminals. We recall that ETS surgery will lower both. The authors find significant neural release of NE in all of the immune organs.
Which immune organs are denerved in thoracic sympathectomy? Does it follow the skin pattern? What types of changes in function might we expect in the denerved region, and how might these regional changes affect the whole system?

NIH scientist Esther Sternberg is one of the foremost authorities on the role of the autonomic nervous system in the immune system. She is worth quoting at length:
"Interactions between the immune and nervous systems play an important role in modulating host susceptibility and resistance to inflammatory disease. Neuroendocrine regulation of inflammatory and immune responses and disease occurs at multiple levels:
  • systemically, through the anti-inflammatory action of glucocorticoids released via hypothalamic-pituitary-adrenal axis stimulation;
  • regionally, through production of glucocorticoids within and sympathetic innervation of immune organs such as the thymus;
  • locally, at sites of inflammation.
Recent studies indicate that physiological levels of glucocorticoids are immunomodulatory rather than solely immunosuppressive, causing a shift in patterns of cytokine production from a TH1- to a TH2 type pattern. Interruptions of this loop at any level and through multiple mechanisms, whether genetic, or through surgical or pharmacological interventions, can render an inflammatory resistant host susceptible to inflammatory disease." (Sternberg, 2001 emphasis added)
Sternberg presents ample theoretical justification for the notion that sympathectomy would alter immune function at all three levels - local, regional and systemic. Systemic changes could certainly arise due to the lowered blood catecholamines, and regional function would be altered according to direct denervation of any immune organs innervated via the upper thoracic sympathetic ganglia. Any local response anywhere would encounter the lowered system levels. Local responses in the denerved region would also encounter denerved immune structures, which could be expected to affect inflammation and healing, among other functions.


Thus, in consideration of Elenkov and Sternberg, the CS model predicts:

Prediction: Thoracic sympathectomy will slow skin healing in the denerved area.

Empirical status: Confirmed in rats, unstudied in humans.

A team of Brazilian scientists decided to test the effects of sympathectomy on skin healing. The methods were straightforward. They sympathectomized rats, gave them skin cuts, and reported:
"Sympathetic denervation accelerates wound contraction but delays reepithelialization (skin healing) in rats-. -Sympathetic denervation affects cutaneous wound healing, probably by a decrease in neurogenic inflammation during the initial phase of healing and the absence of catecholamines throughout the final phase." (Souza et al. 2005)

Tumor Necrosis Factor

Tumor Necrosis Factor, or TNF, is a cytokine which helps to kill malignant tumors. Our Norwegian orthodontists went looking into immune metabolism in rat teeth. They infected rats with bacteria which causes sores. They did a one-sided sympathectomy, to see if they could infer the role of the sympathetic nerves here. The result was that sympathetic nerves have an inhibitory effect on IL-1alpha . . .and a stimulatory effect on TNF-alpha in the intact rat pulp. (Bletsa et al. 2004)

Prediction: Thoracic sympathectomy will reduce the production of Tumor Necrosis Factor.

Empirical status: Confirmed in rats, unstudied in humans.

"We showed that IL-1alpha was increased but not TNF-alpha . . .on the sympathectomized side. Both IL-1alpha and TNF-alpha were expressed in unexposed pulp. TNF-alpha was significantly decreased in the denervated incisor pulp, whereas the level of IL-1alpha remained unchanged." (Bletsa et al. 2004, emphasis added)

"Accumulating evidence suggests that the sympathetic nervous system modulates inflammatory responses and bone remodeling."(Haug et al. 2003)
Prediction: Thoracic sympathectomy will increase the rate at which tumors develop.

Empirical status: Confirmed in rats, unstudied in humans.

"Tumor onset time following implantation of MNB cells was significantly increased in animals sympathectomized as either neonates or as adults." (Fink et al. 1987)