The Submandibular Gland: A Key Organ in the Neuro-Immuno-Regulatory Network?

Abstract

The evidence for the integration of the submandibular gland (SMG) into the neuroimmunoregulatory network has been reviewed. In laboratory rodents, factors extracted from the SMG were shown to stimulate lymphocyte proliferation, to affect the weight of the thymus, spleen and lymph nodes and to induce immunosuppression in several in vivo animal models. The SMG produces significant quantities of nerve growth factor (NGF), epidermal growth factor (EGF), transforming growth factor-β and kallikreins, which are secreted into the saliva and affect immune and mucosal tissues and nerve endings in the gastrointestinal tract. These factors play a role in regulating mucosal immuno/inflammatory response and in regeneration and healing. The major salivary glands also produce antimicrobial proteins and secretory IgA antibodies which are essential factors in mucosal host defense. SMG-derived NGF, EGF and glandular kallikrein are delivered into the bloodstream where they may act as important systemic immunoregulators and also have major regulatory influences on the central neuroendocrine system. There is evidence to indicate that EGF is involved in the regulation of gonadal function. Growth hormone, prolactin, androgens, thyroid hormone and corticosteroids regulate protein synthesis in the SMG, whereas secretory activity is regulated by sympathetic (α- and β-adrenergic) parasympathetic (muscarinic) and peptidergic (substance P and vasoactive intestinal peptide) nerve fibers. Fluid and electrolyte secretion is promoted by parasympathetic, whereas protein secretion is stimulated by sympathetic nerve impulses. Steroid hormones and cytokines (interleukin-1α, -β, tumor necrosis factor, interferon-γ) have a major regulatory influence on protein secretion, including the secretion of immunoglobulin into the saliva. The SMG interacts with the mucosal and systemic compartments of the immune system, with the central and peripheral nervous systems, with the pituitary gland, and with peripheral endocrine organs. These interactions enable the SMG to exert regulatory influences on immune/inflammatory reactions in the gastrointestinal tract, in the lungs, and possibly elsewhere. It is suggested that these functions make this gland a key regulatory organ in the neuroimmunoregulatory network. Evidence is increasing that the major salivary glands fulfill similar functions in other species, including humans.

Continuous combined intake of polydextrose and lactitol stimulates cecal fermentation and salivary IgA secretion in rats

“…Given that the increase of SCFA levels in the intestinal tract affects the activity of autonomic nerves (30,43,44), which in turn should promote the function of salivary glands (45), the stimulation of fermentation and SCFA production by PDX and lactitol in the cecum should affect the activity of autonomic nerves and induce the secretion of salivary IgA. Therefore, further experiments are needed to clarify the relationship between SCFA production in the large intestine and the increase in salivary IgA through the activity of autonomic nerves, which should provide insights into the mechanisms underlying the resistance to upper respiratory tract infections.…”

Salivary IgA as a Useful Non-Invasive Marker for Restraint Stress in Pigs

“…The parotid gland secretes mainly fluid and electrolyte components of saliva and is regulated by PNS impulses [7]. The submandibular and sublingual glands are mixed glands, and secretion of the protein component of saliva is enhanced by SNS impulses [22]. Carpenter et al, reported that the secretion of IgA into saliva was affected by a polymeric immunoglobulin receptor (pIgR)-mediated mechanism in response to autonomic stimulation [3,4], and parotid cells and submandibular cells were differently responded to alpha-and beta-adrenergic stimuli in rat model [4].…”

Salivary MUC5B-Mediated Adherence (Ex Vivo) of Helicobacter pylori During Acute Stress

“…The release of salivary proteins is mainly governed by the synergistic actions of both the sympathetic and parasympathetic branches of the autonomic nervous system (73,74) and is also modulated by several neuropeptides that are released in conjunction with the conventional transmitters acetylcholine and noradrenaline (75,76). Therefore, stress-induced autonomic activation is the most likely explanation for the observed release of MUC5B.…”