A molecular basis for interactions between the immune and neuroendocrine systems

Homeostatic and psychologic alterations associated with infections and tumors are very interesting yet poorly understood pathophysiologic responses. Numerous anecdotal and indirect examples suggest that these responses occur through a link between the central nervous and immune systems (for review see Blalock, Bost, & Smith, 1985; Spector & Korneva, 1981; Maestroni & Pierpaoli, 1981; Felton et al., 1985; Jankovic, 1985). Interactions between the two systems are just now being described. One possible mechanism is direct modulation of the immune system by the sympathetic nervous system. This could occur in innervated immune organs such as spleen, thymus, and bone marrow (Felton et al., 1985). The evidence for this is that sympathectomy and lesioning of specific regions of the brain can be shown to both enhance and/or suppress immune responses (Miles et al., 1985; Roszman et al., 1985). Also, the firing rate of hypothalamic neurons is altered during an immune response (Besedovsky et al., 1977). Alternatively, hormonal involvement in immune reactions has been known for some time, in particular the immunosuppressive effects of glucocorticoids (for review see Cupps & Fauci, 1982). Recently, we and others found that neuroendocrine peptide hormones will modulate T and B lymphocytes plus other immunocyte responses (Besedovsky et al., 1977; Cupps & Fauci, 1982; Johnson et al., 1982; Wybran et al., 1979; Hazum, Chang & Cuatrecasas, 1979; O'Dorisio et al., 1981; Gilman et al., 1982; McCain et al., 1982; Mathews et al., 1983; Plotnikoff et al., 1985; Johnson et al., 1984). Furthermore, lymphocytes themselves can synthesize biologically active neuroendocrine hormones (Blalock & Smith, 1980; O'Dorisio et al., 1980; Smith & Blalock, 1981; Smith et al., 1983; Lolait et al., 1984; Ruff & Pert, 1984), as well as possess specific hormone receptors (Blalock et al., 1985; Johnson et al., 1982; Wybran et al., 1979; Hazum et al., 1979; O'Dorisio et al., 1981; Lopker et al., 1980; Payan, Brewster & Goetzl, 1984; Pert et al., 1985). Immune responses (Besedovsky, del Rey & Sorkin, 1981), thymic hormones (Healy et al., 1983), and lymphokines (Lotze et al., 1985; Woloski et al., 1985) have all been shown to exert hormonal effects. Thus, another method for communication between the immune and neuroendocrine systems seems to be through soluble factors such as neuroendocrine hormones. This review will concentrate on the latter topic, in particular on work this laboratory has done over the past few years to show the lymphocyte production and immunoregulatory actions of neuroendocrine hormones.