CommentariesRegulation of cytokine and chemokine production by transmitters and co-transmitters of the autonomic nervous system
Section snippets
Release of transmitters of the sympathetic nervous system in the vicinity of immune cells
The autonomic nervous system consists of two major components that originate in the CNS: the sympathetic and parasympathetic division. The sympathetic division sets out from nuclei within the brainstem and gives rise to preganglionic efferent fibers that terminate in the paravertebral or prevertebral ganglia. The postganglionic noradrenergic fibers innervate a wide variety of target organs including the heart, gastrointestinal tract, blood vessels, and lymphoid organs. These fibers give rise to
Role of adrenergic receptors in the modulation of cytokine, chemokine, and free radical production
The catecholamines NE and EPI exert their effects by binding to 7 transmembrane spanning G-protein-coupled cell surface receptors termed adrenoceptors. Adrenoceptors can be classified into three major groups: α1-, α2-, and β-adrenoceptor types. Each of these three major types can be subdivided further into at least three subtypes: α1A, α1B, α1C; α2A, α2B, α2C; and β1, β2, and β3.
Regulation of cytokine and no production by purinoreceptors
Immune cells express plasma membrane receptors for extracellular ATP and ADO. Receptors for ATP are termed P2 purinoceptors, while ADO-sensitive receptors are called P1 or ADO receptors. Both ATP and ADO can be present at physiologically relevant concentrations in the vicinity of immune cells 74, 75, 76 and can exert their effects at various subtypes of purinoceptors. ATP receptors are classified as metabotropic (G-protein-coupled) P2y or ionotropic (ion channel) P2x receptors. ADO interacts
Endotoxic shock
The management of severe sepsis includes the administration of ligands of both α- and β-adrenoceptors, aiming to provide cardiovascular support. Such support includes the administration of α-adrenergic agonists to maintain perfusion pressure, and the use of β-adrenergic agonists to improve cardiac output. As discussed above, accumulating evidence shows that these agents can affect the production of inflammatory mediators, which are responsible for the deleterious effects of shock-inducing
Conclusions
Immune cells express various adrenergic and purinergic receptors that are sensitive to transmitters of the SNS. The production of immune/inflammatory mediators (cytokines, chemokines, and free radicals) is modulated by activation of these receptors. The investigations are only at the initial stages of exploring the complex regulation of the production of pro- and anti-inflammatory mediators by various receptor subtypes of the adrenergic and purinergic receptors. Continuing work in this area is
References (111)
- et al.
Neurochemical, electrophysiological and immunocytochemical evidence for a noradrenergic link between the sympathetic nervous system and thymocytes
Neuroscience
(1995) - et al.
Presynaptic receptors involved in the modulation of release of noradrenaline from the sympathetic nerve terminals of the rat thymus
Immunol Lett
(1995) - et al.
Presynaptic modulation of release of noradrenaline from the sympathetic nerve terminals in the rat spleen
Neuropharmacology
(1991) - et al.
Arterial baroreflexes are not essential in mediating sympathoadrenal activation in conscious endotoxic rats
J Auton Nerv Syst
(1992) - et al.
Modulation of immune cell function by the autonomic nervous system
Pharmacol Ther
(1997) - et al.
Intestinal formation of hypoxanthine and uric acid during endotoxemia
J Surg Res
(1997) - et al.
Evidence for adenosine triphosphate degradation in critically-ill patients
Chest
(1985) - et al.
Demonstration that circulating human blood cells have no detectable alpha1-adrenergic receptors by radioligand binding analysis
J Allergy Clin Immunol
(1984) - et al.
Functional α1-adrenergic receptors on leukocytes of patients with polyarticular juvenile rheumatoid arthritis
J Neuroimmunol
(1996) - et al.
Modulation of lipopolysaccharide-induced tumor necrosis factor-α production by selective α- and β-adrenergic drugs in mice
J Neuroimmunol
(1995)
Effect of the PDE III inhibitor amrinone on cytokine and nitric oxide production in immunostimulated J774.1 macrophages
Eur J Pharmacol
Calcium channel blockers and dantrolene differentially regulate the production of interleukin-12 and interferon-γ in endotoxemic mice
Brain Res Bull
The effect of norepinephrine on endotoxin-mediated macrophage activation
J Neuroimmunol
Regulation of macrophage-derived tumor necrosis factor production by modification of adrenergic receptor sensitivity
J Neuroimmunol
Isoproterenol inhibits IL-10, TNF-α, and nitric oxide production in RAW 264.7 macrophages
Brain Res Bull
β2-Adrenergic activation enhances interleukin-8 production by human monocytes
J Neuroimmunol
β-Adrenergic receptors mediate in vivo the adrenaline inhibition of lipopolysaccharide-induced tumor necrosis factor release
Immunol Lett
Stimulation of β-adrenoceptors inhibits endotoxin-induced IL-12 production in mice
J Neuroimmunol
The P2Z purinoreceptor: An intriguing role in immunity, inflammation and cell death
Immunol Today
Activation of adenosine A3 receptors on macrophages inhibits tumor necrosis factor-α
Eur J Pharmacol
Regulation of inducible nitric oxide synthase expression by macrophage purinoreceptors and calcium
J Biol Chem
Pharmacology of adenosine A2A receptors
Trends Pharmacol Sci
Inhibition of human monocyte TNF production by adenosine receptor agonists
Life Sci
β-Adrenergic agonists suppress chronic/relapsing experimental allergic encephalomyelitis (CREAE) in Lewis rats
J Neuroimmunol
Thymus and adrenals in the response of the organism to injuries and intoxications
Br J Exp Pathol
Changes in blood hormone levels during the immune response
Proc Soc Exp Biol Med
Vasoactive hormones in endotoxin shockA comparative study in cats and dogs
J Physiol (Lond)
Pharmacology of cotransmission in the autonomic nervous systemIntegrative aspects on amines, neuropeptides, adenosine triphosphate, amino acids and nitric oxide
Pharmacol Rev
Neural release of ATP and adenosine
Ann NY Acad Sci
Sympathetic innervation of murine thymus and spleenA comparative histofluorescence study
Anat Rec
Autonomic nervous system innervation of thymic-related lymphoid tissue in wildtype and nude mice
J Comp Neurol
Noradrenergic and peptidergic innervation of lymphoid tissue
J Immunol
β-Adrenoceptor-mediated effects in rat cultured thymic epithelial cells
Br J Pharmacol
Noradrenergic sympathetic innervation of lymphoid organs
Prog Allergy
Mechanisms involved in the rapid dissipation of plasma epinephrine response to bacterial endotoxin in conscious rats
Am J Physiol
CNS biogenic amines and the immune system
Immune-neuroendocrine interactions
J Immunol
Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides
Am J Physiol
Breakdown of adenine nucleotides, formation of oxygen free radicals, and early markers of cellular injury in endotoxic shock
Eur J Surg
The biological role of adenosine for the cellular function during sepsis
Prog Appl Microcirc
Concentration of purine compounds in the cerebrospinal fluid of infants suffering from sepsis, convulsions and hydrocephalus
J Perinat Med
Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones
Science
Immune-neuro-endocrine interactionsFacts and hypotheses
Endocr Rev
Mechanism of interleukin 12-mediated toxicities during experimental viral infectionsRole of tumor necrosis factor and glucocorticoids
J Exp Med
Macrophage inflammatory protein-1A prostaglandin-independent endogenous pyrogen
Science
The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation
N Engl J Med
Neuroendocrine-immune system interactions and autoimmunity
Annu Rev Immunol
Neural-immune interactions in health and disease
J Clin Invest
Catecholamine influences and sympathetic neural modulation of immune responsiveness
Annu Rev Pharmacol Toxicol
Enhancement of the murine primary antibody response by phenylephrine in vitro
Drug Chem Toxicol
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A chicken and egg scenario in psychoneuroimmunology: Bidirectional mechanisms linking cytokines and depression
2021, Journal of Affective Disorders ReportsCitation Excerpt :Given that clinical studies generally have not examined the cytokine-SNS relationship in depressed patients, we will primarily review theoretical and pre-clinical evidence, and future studies should attempt to examine clinical associations of SNS activation with cytokine activity. At both systemic and more localized zones of inflammation, acute activation of the SNS results in suppression of cytokines such as IL-1β and TNFα via transcription factors such as NF-kβ in microglia and peripheral macrophages, likely mediated by β2 adrenergic receptor binding per preclinical models (Haskó and Szabó, 1998; Nance and Sanders, 2007; Scanzano and Cosentino, 2015). However, chronic activation of the SNS may be associated with β adrenergic mediated transcription of pro-inflammatory cytokines such as IL-6 (Ramirez et al., 2016; Rohan Walker et al., 2013).
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Corresponding author: Dr. Csaba Szabó, Children’s Hospital Medical Center, Division of Critical Care, 3333 Burnet Ave., Cincinnati, OH 45229 [Tel. (513) 636-8714; FAX (513) 636-4892].