Norepinephrine, the β-Adrenergic Receptor, and Immunity

Autonomic innervation and regulation of the immune system (1987–2007)

“…To date, a number of clinical examples support a role for a neuroimmune interrelationship in the etiology or progression of a disease state, and many of these examples are discussed thoroughly in a number of excellent reviews (Glaser, 2005;Heijnen and Cohen, 1999;Sanders and Straub, 2002). All of these reviews emphasize that an understanding of the cellular, biochemical, and molecular mechanisms by which NE regulates the level of immune cell activity will one day lead to the development of therapeutic approaches that will alter the etiology and/or progression of immune system-related diseases.…”

“…Early in vitro studies using unfractionated CD4+ T cell populations suggested that NE, β 2 ARselective agonists, or other cAMP-elevating agents either inhibited or enhanced the level of IL-2, IFN-γ, or IL-4 produced, while studies using populations of Th1 and Th2 cells suggested that these agents decreased the level of IFN-γ and increased the level of IL-4, respectively [Reviewed extensively in (Kin and Sanders, 2006;Kohm and Sanders, 2001a;Sanders and Straub, 2002). When naive T cells were isolated and activated, IL-2 secretion was decreased by exposure to NE, suggesting that NE and β 2 AR stimulation affected the ability of an activated naive T cell to expand in number.…”

“…The effect of NE-depletion on the primary T cell-dependent antibody response in vivo has also been investigated [reviewed extensively in (Kin and Sanders, 2006;Kohm and Sanders, 2001b;Sanders and Munson, 1985;Sanders and Straub, 2002)]. Data have shown that either a decrease or increase in the Th cell-dependent IgM antibody response occurs after NE depletion.…”

Stress-induced remodeling of lymphoid innervation

“…Structural varicosities situated periodically over the length of these catecholaminergic fibers release micromolar concentrations of NE in response to stress and other stimuli (Shimizu, Hori et al 1994;Madden, Sanders et al 1995;Bellinger, Lorton et al 2001). NE signals leukocytes via cellular β-adrenergic receptors, which activate the cAMP/PKA signaling cascade to alter antigen presentation, cellular activation, cytokine production, cell trafficking, and effector activities such as cellular cytotoxicity and antibody production (Kammer 1988;Ottaway and Husband 1994;Madden, Sanders et al 1995;Carlson, Fox et al 1997;Panina-Bordignon, Mazzeo et al 1997;Sanders and Straub 2002;SaintMezard, Chavagnac et al 2003). Effects on cytokine response are especially pronounced, with many studies suggesting that sympathetic activation can inhibit the expression of proinflammatory cytokines (Sanders and Kavelaars 2007), suppresses Th1 cytokines in favor of a Th2 profile (Panina-Bordignon, Mazzeo et al 1997;Cole, Korin et al 1998;Kohm and Sanders 1999;Maestroni and Mazzola 2003;Sanders and Kavelaars 2007), and inhibit the expression of Type I interferons (Collado-Hidalgo, Sung et al 2006).…”

Is Psychological Stress a Possible Risk Factor for Periodontal Disease? A Systematic Review

“…The biological mechanism involves the autonomous nervous system (ANS) which, when stimulated by adrenergic receptors, leads to secretion of catecholamines (adrenalin/noradrenalin) (CAs), neuropeptides such as substance P (SP) [18] and chromogranin A (CgA) by the adrenal medulla, thereby indirectly provoking periodontal tissue breakdown. Catecholamines regulate the immune response by stimulation of immune cell propagation and activity [19,20], whereas CgA have antimicrobial effects [21]. The autonomous nervous system acts on the salivary glands during stress by secreting enzymes such as salivary alpha-amylase (sAA), which acts by neutralizing and preventing pathogens from entering the body via the mucosal surfaces and inhibiting the adherence and growth of bacteria in the oral cavity [22,23].…”