Stress & The Immune System: Potential Adaptive Ramifications
Firdaus S. Dhabhar
,
Section of Oral Biology
College of Dentistry
The Ohio State University, Columbus, OH
When a gazelle sees a charging lion, the gazelle's brain detects a threat and orchestrates a physiologic response which first prepares, and then enables, the gazelle to flee. Most evolutionary selection pressures are stressors, and one of the primary functions of the brain is to perceive stress, warn the body of danger, and enable an organism to protect itself. Keeping in mind this evolutionary reasoning, and contrary to the widely held belief that stress is immunosuppressive, we initially hypothesized that just as the stress response prepares the nervous, cardiovascular, and musculoskeletal systems for fight or flight, under certain conditions it may also prepare the immune system for challenges (e.g. wounding or infection) which may be imposed by the stressor.
Experiments were designed to test this hypothesis. Initial studies showed that acute stress induced a significant redistribution of leukocytes from the blood to the skin. Recognizing that the skin is the largest organ in the body and is the major barrier protecting an organism from the environment we hypothesized that this stress-induced redistribution of leukocytes to the skin may be an adaptive response serving to enhance skin immune function during acute stress. This hypothesis was tested using a model for skin delayed type hypersensitivity (DTH) reactions. DTH reactions are antigen-specific, cell-mediated immune responses that, depending on the antigen, mediate beneficial (resistance to viruses, bacteria, fungi) or harmful (allergic dermatitis, autoimmunity) aspects of immunity. Studies showed that acute stress administered immediately before antigen exposure, significantly enhanced skin DTH. In contrast, chronic stress significantly suppressed the immune response. Stress-induced changes in leukocyte distribution were identified as mediators of these bi-directional effects of stress, since acute stress induced a significant mobilization of leukocytes from the blood to the skin while chronic stress suppressed leukocyte mobilization. In order to identify the hormonal mediators of the observed effects of stress, we first showed that adrenalectomy (ADX) eliminated the stress-induced enhancement of DTH. Acute administration (to ADX animals) of low doses of corticosterone and/or epinephrine significantly enhanced skin DTH. In contrast, acute administration of high doses of corticosterone, low doses of dexamethasone, or chronic administration of moderate doses of corticosterone, suppressed skin DTH. Therefore, the timing and duration of stress may significantly affect the nature (enhancing versus suppressive) of the effects of stress on skin immune function. These results suggest that during acute stress, stress hormones may help enhance immune function by informing the immune system about impending challenges (e.g. wounding or infection) which may be imposed by a stressor (e.g. an aggressor). Thus, during acute stress, the brain may send a warning signal to the immune system just as it does to other fight/flight systems in the body.