The short-term stress response - Mother nature's mechanism for enhancing protection and performance under conditions of threat, challenge, and opportunity

Abstract

Our group has proposed that in contrast to chronic stress that can have harmful effects, the short-term (fight-or-flight) stress response (lasting for minutes to hours) is nature's fundamental survival mechanism that enhances protection and performance under conditions involving threat/challenge/opportunity. Short-term stress enhances innate/primary, adaptive/secondary, vaccine-induced, and anti-tumor immune responses, and post-surgical recovery. Mechanisms and mediators include stress hormones, dendritic cell, neutrophil, macrophage, and lymphocyte trafficking/function and local/systemic chemokine and cytokine production. Short-term stress may also enhance mental/cognitive and physical performance through effects on brain, musculo-skeletal, and cardiovascular function, reappraisal of threat/anxiety, and training-induced stress-optimization. Therefore, short-term stress psychology/physiology could be harnessed to enhance immuno-protection, as well as mental and physical performance. This review aims to provide a conceptual framework and targets for further investigation of mechanisms and conditions under which the protective/adaptive aspects of short-term stress/exercise can be optimized/harnessed, and for developing pharmacological/biobehavioral interventions to enhance health/healing, and mental/cognitive/physical performance.

Keywords: Amateur/elite athletes; Armed forces/special operations forces; Eustress/distress; Infection/autoimmune disease/cancer; Performers/entertainers; Psycho-neuro-endocrine-immunology; Sleep; Stress optimization; Stress reduction; Wound healing.

Figure 1. Enhancing versus suppressive effects of stress on immune function and potential consequences for health outcomes

Short-term stress experienced during vaccination, wounding, or infection may enhance immuno-protective responses. Short-term stress experienced during immune activation in response to self/innocuous antigens or allergens, may excerbate pro-inflammatory and autoimmune disorders. Chronic stress-induced increases in pro-inflammatory or Type-2 cytokine mediated immune responses may also exacerbate inflammatory and autoimmune disease. Chronic stress induced suppression of immune responses may decrease the effectiveness of vaccination and wound healing and decrease resistance to infection and cancer. (Reprinted with permission from S. Karger AG, Basel: Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Dhabhar, F.S., NeuroImmunoModulation, 16(5): p300–317, Copyright 2009.)

Figure 2. Steps and factors that mediate the transition from adaptive short-term stress to deleterious chronic stress

Time is represented on the “x” axis and changes in stress-related biological factors are represented on the “y” axis. The upright yellow isosceles triangle (top panel) represents an adaptive short-term stress response. In order for a stress response to be adaptive, it is critical that stress related biological changes occur rapidly (within minutes) and resolve back to baseline rapidly (within minutes to hours). Life involves a series of stress “hits” and responses. Most humans and other organisms are built to handle this series of stress responses and can continue to mount adaptive/protective responses under such conditions especially if their psychological and physiological systems return to baseline/resting conditions (green bars between yellow triangles) between stress hits. The isosceles trapezoid (middle panel) represents a prolonged short-term stress response with delayed shutdown which results in greater overall area under the curve exposure to stress related factors compared to the prototypical adaptive stress response. Such prolonged stress responses can begin to have deleterious effects especially if they are part of a series of stress hits with little or no time of return to baseline/resting conditions between hits. The long red rectangle (bottom panel) is a graphical representation of chronic stress that is known to have numerous deleterious effects on brain, body, and health, and mental and physical performance. An important characteristic of chronic stress is that the stressor(s), stress perception, or aspects of the stress response, persist for long periods (months to years) of time and result in an overall increase in exposure to, and/or sustained changes in, stress-related biological factors. Rather than stress in general, it is chronic stress that suppresses endogenous defenses (such as wound healing and immuno-protective responses), and repair/restoration mechanisms (such as DNA repair, telomere lengthening by telomerase, and anti-oxidant systems), and mental and physical performance.

Figure 3. The Stress Spectrum[3; 6; 11; 32; 205]

We have proposed the concept of the STRESS SPECTRUM to understand, optimize, and harness the beneficial effects of short-term stress, and minimize the harmful effects of chronic stress. One end of the spectrum is represented by GOOD stress that involves a rapid biological stress response mounted in the presence of the stressor, followed by a rapid shut-down of the response upon cessation of the stressor. Such responses induce physiological conditions that are likely to enhance protective immunity, mental and physical performance, and overall health. The opposite end of the spectrum is represented by BAD stress that involves chronic or long-term biological changes that are likely to result in dysregulation or suppression of immune function, a decrease in mental and physical performance, and an increased likelihood of disease. Short- and/or long- term stress is generally superimposed on a psycho-physiological RESTING STATE, or “green zone” of low/no stress that also represents a state of health maintenance/restoration. While the sympathetic nervous system and hypothalamic-pituitary-adrenal axis are the major drivers of the fight-or-flight response, the parasympathetic nervous system is the major driver of recovery from stress. The parasympathetic nervous system, together with negative feedback loops within physiological fight-or-flight systems, drives the rest-and-digest response that mediates recovery from stress and a return to resting state. In order to maintain health one needs to optimize GOOD stress, maximize the RESTING ZONE, and minimize BAD stress. This is likely to involve a multi-pronged approach [3; 6; 11; 32]: Sleep of a quality and duration that helps one feel rested in the morning, a moderate and healthy diet, and consistent and moderate exercise or physical activity, are three LIFESTYLE FACTORS that are likely to enable one to stay on the “good” side of the stress spectrum. Effective perspective-setting, appraisal/reappraisal, and coping mechanisms, social support, authenticity, genuine gratitude, and compassion towards others and oneself, are likely to provide PSYCHO-SOCIAL BUFFERS against bad stress, and to enable one to stay on the “good” side of the stress spectrum. Additionally, depending on individual preferences, ACTIVITIES such as, meditation, yoga, religious beliefs and activities, nature walks or hikes, exercise, dancing, music, art, craft, fishing, painting, etc. may also reduce BAD stress, extend the RESTING ZONE, and optimize GOOD stress. Such personal activities are likely to involve different strokes for different folks and need not always be meditative or reflective in nature. (Reprinted with permission from Springer Nature: Effects of stress on immune function: the good, the bad, and the beautiful. Dhabhar, F.S., Immunologic Research, 58, p 193–210, Copyright 2014.)