Stress, behavior, and immunity: animal models and mediating mechanisms.

Research with animal model systems demonstrates a causal relation between stress and disease susceptibility. The physiological sequelae of stressful stimulation vary with type of stressor, chronicity, and perceived control. Different patterns of endocrine secretion are thus associated with specific behavioral parameters. The immune system is regulated at several levels: genetic, cellular, hormonal, and neuronal. Stress and behavioral factors can modulate both cell-mediated and humoral immunity by impacting on the latter three levels of regulation. Both corticosteroids and catecholamines, released as part of the response to aversive stimulation, profoundly inhibit immune responsivity by binding directly to the lymphocyte surface or by releasing secondary mediators that increase the function of suppressor lymphocytes. In addition, there are direct neuroanatomical connections between the hypothalamus and lymphoid organs. Subtle changes in experimental design have yielded significant differences in results that have increased understanding of intermediary mechanisms. Such research complements psychoneuroimmunological and behavioral epidemiological studies in humans.