Pharmacol Rev. 2000 Dec;52(4):595-638.
Elenkov IJ1, Wilder RL, Chrousos GP, Vizi ES.
Abstract
The
brain and the immune system are the two major adaptive systems of the
body. During an immune response the brain and the immune system "talk to
each other" and this process is essential for maintaining homeostasis.
Two major pathway systems are involved in this cross-talk: the
hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous
system (SNS). This overview focuses on the role of SNS in neuroimmune
interactions, an area that has received much less attention than the
role of HPA axis.
Evidence accumulated over the last 20 years suggests
that norepinephrine (NE) fulfills the criteria for
neurotransmitter/neuromodulator in lymphoid organs. Thus, primary and
secondary lymphoid organs receive extensive sympathetic/noradrenergic
innervation. Under stimulation, NE is released from the sympathetic
nerve terminals in these organs, and the target immune cells express
adrenoreceptors. Through stimulation of these receptors, locally
released NE, or circulating catecholamines such as epinephrine, affect
lymphocyte traffic, circulation, and proliferation, and modulate
cytokine production and the functional activity of different lymphoid
cells. Although there exists substantial sympathetic innervation in the
bone marrow, and particularly in the thymus and mucosal tissues, our
knowledge about the effect of the sympathetic neural input on
hematopoiesis, thymocyte development, and mucosal immunity is extremely
modest.
In addition, recent evidence is discussed that NE and
epinephrine, through stimulation of the
beta(2)-adrenoreceptor-cAMP-protein kinase A pathway, inhibit the
production of type 1/proinflammatory cytokines, such as interleukin
(IL-12), tumor necrosis factor-alpha, and interferon-gamma by
antigen-presenting cells and T helper (Th) 1 cells, whereas they
stimulate the production of type 2/anti-inflammatory cytokines such as
IL-10 and transforming growth factor-beta. Through this mechanism,
systemically, endogenous catecholamines may cause a selective
suppression of Th1 responses and cellular immunity, and a Th2 shift
toward dominance of humoral immunity. On the other hand, in certain
local responses, and under certain conditions, catecholamines may
actually boost regional immune responses, through induction of IL-1,
tumor necrosis factor-alpha, and primarily IL-8 production. Thus, the
activation of SNS during an immune response might be aimed to localize
the inflammatory response, through induction of neutrophil accumulation
and stimulation of more specific humoral immune responses, although
systemically it may suppress Th1 responses, and, thus protect the
organism from the detrimental effects of proinflammatory cytokines and
other products of activated macrophages. The above-mentioned
immunomodulatory effects of catecholamines and the role of SNS are also
discussed in the context of their clinical implication in certain
infections, major injury and sepsis, autoimmunity, chronic pain and
fatigue syndromes, and tumor growth.
Finally, the pharmacological
manipulation of the sympathetic-immune interface is reviewed with focus
on new therapeutic strategies using selective alpha(2)- and
beta(2)-adrenoreceptor agonists and antagonists and inhibitors of
phosphodiesterase type IV in the treatment of experimental models of
autoimmune diseases, fibromyalgia, and chronic fatigue syndrome.
https://www.ncbi.nlm.nih.gov/pubmed/11121511
