Psychoneuroimmunology for the psychoneuroendocrinologist: a review of animal studies of nervous system-immune system interactions.

Evidence for interactions between the nervous and immune systems arises from a number of experimental observations: the behavioral conditioning of immune responses, the effects of stimulation or lesion of brain sites on immune system function, the effects of stressors on immune responses and tumor growth, and physiological and neurochemical changes in the brain during immune responses. The links between the nervous and immune systems probably include glucocorticoids secreted from the adrenal gland, catecholamines and neuropeptides secreted by sympathetic terminals and the adrenal medulla, certain pituitary and gonadal hormones, and polypeptides produced by cells of the immune system. The effect of glucocorticoids is not exclusively immunosuppressive, nor is it adequate to explain all the effects of stress. The effects of opiates on immune function are complex; in vitro, endogenous opiates most often facilitate immune activity, but in vivo, opiates appear to inhibit immune responses and impair tumor rejection. The in vitro effects are rarely prevented by naloxone pretreatment and appear to require the integrity of the C- rather than the N-terminal of beta-endorphin, suggesting a nonopiate character. Infections or the administration of antigens increase circulating concentrations of glucocorticoids and activate cerebral catecholaminergic metabolism, especially in the hypothalamus. These responses suggest that challenges to the immune system are physiologic stressors. Interleukin-1 (IL-1) produced by immune cells may be the mediator of these effects, thus acting as an "immunoneurotransmitter". The cerebral responses suggest that the brain can monitor the progress of immune responses. IL-1 and the glucocorticoids together may form a regulatory feedback mechanism for immune responses.