Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection and Immunopathology

By F. Dhabhar. Neuroimmunomodulation, 2009

868 citations recorded by the source corpus.

Stress is known to suppress immune function and increase susceptibility to infections and cancer. Paradoxically, stress is also known to exacerbate asthma, and allergic, autoimmune and inflammatory diseases, although such diseases should be ameliorated by immunosuppression. Moreover, the short-term fight-or-flight stress response is one of nature’s fundamental defense mechanisms that enables the cardiovascular and musculoskeletal systems to promote survival, and it is unlikely that this response would suppress immune function at a time when it is most required for survival (e.g. in response to wounding and infection by a predator or aggressor). These observations suggest that stress may suppress immune function under some conditions while enhancing it under others. The effects of stress are likely to be beneficial or harmful depending on the type (immunoprotective, immunoregulatory/inhibitory, or immunopathological) of immune response that is affected. Studies have shown that several critical factors influence the direction (enhancing vs. suppressive) of the effects of stress or stress hormones on immune function: (1) Duration (acute vs. chronic) of stress: Acute or short-term stress experienced at the time of immune activation can enhance innate and adaptive immune responses. Chronic or long-term stress can suppress immunity by decreasing immune cell numbers and function and/or increasing active immunosuppressive mechanisms (e.g. regulatory T cells). Chronic stress can also dysregulate immune function by promoting proinflammatory and type-2 cytokine-driven responses. (2) Effects of stress on leukocyte distribution: Compartments that are enriched with immune cells during acute stress show immunoenhancement, while those that are depleted of leukocytes, show immunosuppression. (3) The differential effects of physiologic versus pharmacologic concentrations of glucocorticoids, and the differential effects of endogenous versus synthetic glucocorticoids: Endogenous hormones in physiological concentrations can have immunoenhancing effects. Endogenous hormones at pharmacologic concentrations, and synthetic hormones, are immunosuppressive. (4) The timing of stressor or stress hormone exposure relative to the time of activation and time course of the immune response: Immunoenhancement is observed when acute stress is experienced at early stages of immune activation, while immunosuppression may be observed at late stages of the immune response. We propose that it is important to study and, if possible, to clinically harness the immunoenhancing effects of the acute stress response, that evolution has finely sculpted as a survival mechanism, just as we study its maladaptive ramifications (chronic stress) that evolution has yet to resolve. In view of the ubiquitous nature of stress and its significant effects on immunoprotection as well as immunopathology, it is important to further elucidate the mechanisms mediating stress-immune interactions and to meaningfully translate findings from bench to bedside.

Subfields: Behavioral Neuroscience, Nutrition and Dietetics, Rehabilitation

View Paper: https://www.semanticscholar.org/paper/9a4bc36245c64b84d489161e282660b3ccabe60a

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Citations in the corpus

Marine Ecosystem Assessment for the Southern Ocean: Birds and Marine Mammals in a Changing Climate (2020, background): “…increased stress in wildlife populations, which contributes to disease outbreaks (Lafferty and Holt, 2003) and threatens immunocompetence (Tarszisz et al., 2014) via its oftendevastating consequences on the immune system (e.g., Dhabhar, 2009) and can be a significant factor in disease expression.”
Neurobiological and Systemic Effects of Chronic Stress (2017, background): “damage,’’ is in the immune system, in which an acute stressor activates an acquired immune response via mediation by catecholamines and glucocorticoids and locally produced immune mediators; and, yet, a chronic exposure to the same stressor over several weeks has the opposite effect and results in i”
Ranavirus Ecology and Evolution: From Epidemiology to Extinction (2015, background): “…chronically elevated levels of glucocorticoid “stress” hormones have negative impacts on the immune system, such as reducing circulating lymphocyte populations, decreasing cytokine production, or suppressing cell-mediated immune responses (Sheridan et al. 1994 ; Haddad et al. 2002 ; Dhabhar 2009 ).”
Sleep and immune function (2011, background): “to the skin, concomitant with a drop in their circulating numbers [16, 27].”
From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression (2014, background): “When mobilized, this response is associated with enhanced postinjury wound healing and recovery, which can be critical for survival (Dhabhar, 2009; Rosenberger et al., 2009).”
Rethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters. (2018, neutral): “More recently, this picture has been complicated by findings suggesting that cortisol may both enhance and suppress inflammation following acute stress, and do so in a time- and concentrationdependent manner (Cain and Cidlowski, 2017; Dhabhar, 2009).”
Escape from the pond: stress and developmental responses to ranavirus infection in wood frog tadpoles (2011, background): “…measure variables associated with immune outcome in this study, previous work in amphibians and other vertebrates suggest that the HPI axis stimulates the immune system (Rollins-Smith 2001; Haddad, Saadé & Safieh-Garabedian 2002; Demas 2004; Viswanathan, Daugherty & Dhabhar 2005; Dhabhar 2009).”