Catecholamines immune activation

Altered Catecholamine Availability with Immune Activation... 

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. 

Catecholamines from non-neuronal intracellular and extracellular sources can interact with cells of the immune system. Recently, NE and EPI that can be released by activating stimuli have been detected in lymphocytes and macrophages [reviewed in 2], These cells may synthesize catecholamines and/or take up and store catecholamines from extracellular sources (i.e., NE released from sympathetic nerves or NE and EPI present in the plasma). 

NE and EPI stimulate a- and (TAR on the cell surface of target tissues. P2-AR are expressed on almost all types of immune cells, with the notable exception of T-helper (Th)2 clones [3], P-AR on immunocytes are coupled with Gs proteins and adenylate cyclase, with subsequent activation increasing intracellular adenosine 3 , 5 -cyclic monophosphate (cAMP) and protein kinase A (PKA). Under normal conditions, P-AR cell surface expression up- and down-regulates in response to reduced and increased catecholamine... 

Nonimmune stresses can increase circulating proinflammatory cytokine concentrations. Hemorrhage, and certain psychological and physical stresses all increase HPA activity through mechanisms that may include catecholamines and peripheral CRH [reviewed in 29], However, in some experiments correlations between plasma ACTH and IL-6 levels in models of immune and nonimmune stresses are low. The role played by cytokines in the ACTH response to nonimmune stresses has not been established. 

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. 

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