Immunoregulation by the salivary glands

Abstract

The evidence for the integration of the submandibular gland (SMG) into the neuroimmunoregulatory network is 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 and in vitro models. The SMG produces significant amount of nerve growth factor (NGF), epidermal growth factor (EGF), transforming growth factor-β, and kallikreins. These factors are secreted into the saliva and affect immune and mucosal tissues and nerve endings in the gastrointestinal tract. They may thus play a role in the regulation of mucosal immune/inflammatory responses. 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 exert regulatory influences on the neuroendocrine system. Growth hormone, prolactin, androgens, thyroid hormone and corticosteroids regulate protein synthesis in the SMG, where as secretory activity is regulated by sympathetic, parasympathetic and peptidergic nerve fibers. Steroid hormones and cytokines as interleukin-1α, -1β, tumor necrosis factor-α, interferon-γ have 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. Biomedical Reviews 1998; 9: 79-91.