Sympathetic nervous system aging

The sympathetic nervous system (SNS) and the hypothalamic-pituitary axis work together as important modulators of the immune system after exposure to stressors. Norepinephrine (NE) and epinephrine (EPI) (catecholamines from the SNS) and neuroendocrine hormones modulate a range of immune cell activities, including cell proliferation, cytokine and antibody production, lytic activity, and migration. This chapter will focus on these two major pathways of brain-immune signaling, briefly summarizing the evidence for SNS and hypothalamic-pituitary-adrenal (HPA) modulation of immune function, their influence on immune-mediated diseases, immune modulation in aging, and early life influences on these pathways. 

Cancer is uncommon during the first two decades of life, but is nonetheless a substantial concern. In the United States, cancer is diagnosed in approximately 12 400 children and adolescents annually and is the most common cause of death from any kind of disease between 1 and 19 years of age. In the United States and other developed countries, lymphoid neoplasms (leukaemia, lymphoma) and cancers of the central nervous system are the most common paediatric malignancies. Other kinds of childhood tumours include embryonal tumours of the retina, sympathetic nervous system, kidney, and liver tumours of bone and soft connective tissues and certain gonadal neoplasms. Different kinds of cancer (e.g. carcinomas of liver or thyroid) may predominate in children in parts of the world where specific environmental risk factors are more prevalent. 

Two Japanese primigravidae, aged 25 and 28 years, developed the HELLP syndrome, a severe variant of preeclampsia in which there is Hemolysis, Elevated Liver enzymes, and a Low Platelet count (4). They were given parenteral hyoscine butylbromide for abdominal pain and had seizures 60-90 minutes later. One died from intracerebral hemorrhage some days later and the other survived after a cesarean section soon afterward. The authors speculated that anticholinergic drugs may enhance sympathetic nervous system activity, and in particular vasoconstriction, and should be avoided in pre-eclampsia. It is not clear how widespread their use is... 

Propofol is a cardiodepressant and resets the baroreflex set-point, with a tendency to bradycardia (which occurs in some 5% of cases), hypotension (16%), or both (1.3%) (8). The hypotension may be brought about by peripheral vasodilatation, reduced myocardial contractility, and inhibition of sympathetic nervous system outflow (9). Four deaths due to cardiovascular collapse during induction have been reported in patients aged 78-92 years given propofol 1.1-1.8 mg/kg (10). The patients were of ASA classes 3 or 4. 

Some cases also show dyscontrol of autonomic functions mediated by the potentially affected central noradrenergic sympathetic nervous system, with losses of norepinephrine neurons of the locus coeruleus (4). There can also be variable late neuropsychiatric disturbances that sometimes progress to a debilitating state and eventual fatality (2, 5, 6). Dementia is about six times more frequent in elderly patients with PD than without it (5). Major depression also occurs in PD, and psychosis is sometimes associated with DA agonist therapy (5-7). Mortality is 2-5-times higher among PD patients than in age-matched non-affected persons, and life expectancy is greatly reduced (8). 

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