Sympathetic nervous system immunity

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. 

Schorr, E. and Arnason, B., Interactions between the sympathetic nervous system and the immune system, Brain Behav. Immun., 13, 271, 1999. 

O Rourke J, Cone RE The induction of splenic suppressor T ceUs through an immune-privileged site requires an intact sympathetic nervous system. J Neuroimmunol 2004 153 40-49. 

In the ebb phase, there is increased activity of the sympathetic nervous system and increased plasma levels of adrenaline and glucocorticoids but a decreased level of insulin. This results in mobilisation of glycogen in the liver and triacylglycerol in adipose tissue, so that the levels of two major fuels in the blood, glucose and long-chain fatty acids, are increased. This is, effectively, the stress response to trauma. These changes continue and are extended into the flow phase as the immune cells are activated and secrete the proinflammatory cytokines that further stimulate the mobilisation of fuel stores (Table 18.2). Thus the sequence is trauma increased endocrine hormone levels increased immune response increased levels of cytokines metabolic responses. 

The opioids may modulate the actions of the immune system by effects on lymphocyte proliferation, antibody production, and chemotaxis. Natural killer cell cytolytic activity and lymphocyte proliferative responses to mitogens are usually inhibited by opioids. Although the mechanisms involved are complex, activation of central opioid receptors could mediate a significant component of the changes observed in peripheral immune function. In general, these effects are mediated by the sympathetic nervous system in the case of acute administration and by the hypothalamic-pituitary-adrenal system in the case of prolonged administration of opioids. 

The brain and the immune system are accepted as the two major body s adaptive systems (Elenkov et al., 2000). The brain can modulate immune functions and the immune system also sends messages to the brain. The communication between these two systems is done mainly by the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). The sympathetic nervous system (SNS), which is part of the ANS, innervates the lymphoid organs (Elenkov et al., 2000) (Flierl et al., 2007). Catecholamines, like dopamine, serotonin, epinephrine and norepinephrine, are the end products of the SNS. 

Hasko G (2001) Receptor-mediated interaction between the sympathetic nervous system and immune system in inflammation. Neurochem. Res. 26 1039-1044. 

Sympathetic Nervous System Interaction with the Immune System... 

The activation of the stress systems affects all tissues of the organism, and the peripheral immune system is no exception. These effects are mediated through at least tw o pathways via the HPA axis and by virtue of the innervation of lymphatic tissues by autonomic nerve fibers, especially from the sympathetic nervous system. All lymphoid tissues, primary (bone marrow and thymus) as well as secondary (spleen, lymph nodes, and gut-associated lymphoid tissue) are innervated by sympathetic nerve fibers. As discussed above, most lymphoid cells express catecholamine receptors, including B-lymphocytes, CD4- and CD 8-positive T cells, dendritic cells, monocytes, and macrophages. 

The sympathetic nervous system innervates the major lymphoid organs such as the spleen with nerve fibers reaching both the vasculature and the parenchyma where lymphocytes, primarily T cells (T helper type 1-2, T l, T j2), reside (Friedman and Irwin, 1997). T cells possess receptors for both norepinephrine and neuropeptide Y that are released in response to sympathetic nerve stimulation. The adrenergic receptors are primarily the subtype, which is consistent with data demonstrating that (32 agonists can markedly influence the immune system (Kohm and Sanders, 2001). For example, stimulation of T cell receptors results in increased cyclic AMP formation, which can modulate cytokine expression, i.e., decreasing... 

Stroke induces an acute stress response—i.e., over-activation of the sympathetic nervous system and increased corticosteroid levels (with resultant neutrophiha and lymphocytopenia). This in turn leads to depressed immunity and altered immune responses during the acute phase of stroke and may predispose patients to infections, particularly pneumonia, which is the commonest cause of mortality after the first few days of stroke (Meisel et al., 2005). In the clinical setting, increased total white cell counts and neutrophilia, which correlate with infarct size, are independently associated with worse outcome after stroke. Recently a massive and early activation of the systemic immnne system has been shown to occur also in experimental stroke (Offner et al., 2006). 

It is now generally accepted that emotional/psychological stress stimulates the sympathetic nervous system, which in turn can lead to abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis [7]. During normal or abnormal times the HPA axis serves as a communicator between nervous, immune and endocrine systems. Thus, during stressful conditions abnormal secretions occur that can produce a variety of adverse effects upon various health states [7,8]. 

Psychological stress may influence the immune system by activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary axis (SAM). The well-described innervation of primary and secondary lymphoid tissues by the autonomic nervous system also has been implicated in stress-related modulation of the immune response. These pathways operate by producing biological mediators that interact with and affect cellular components of the immune system.13... 

Smooth muscle relaxation, central nervous system (CNS) excitation, and cardiac stimulation are the principal pharmacological effects observed in patients treated with theophylline. The action of theophylline on the respiratory system is easily seen in the asthmatic by the resolution of obstruction and improvement in pulmonary function. Other mechanisms that may contribute to the action of theophylline in asthma include antagonism of adenosine, inhibition of mediator release, increased sympathetic activity, alteration in immune cell function, and reduction in respiratory muscle fatigue. Theophylline also may exert an antiinflammatory effect through its ability to modulate inflammatory mediator release and immune cell function. 

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