Enhancing versus Suppressive Effects of Stress on Immune Function Implications for Immunoprotection versus Immunopathology.docVIP

ORIGINAL ARTICLE EnhancingversusSuppressiveEffectsofStressonImmune Function:ImplicationsforImmunoprotectionversus Immunopathology FirdausS.Dhabhar,PhD It is widely believed that stress suppresses immune function and increases susceptibility to infections and cancer. Paradoxically, stressisalsoknowntoexacerbateallergic,autoimmune,andinflammatorydiseases.Theseobservationssuggestthatstressmay havebidirectionaleffectsonimmunefunction,beingimmunosuppressiveinsomeinstancesandimmunoenhancinginothers.Ithas recently been shown that in contrast to chronic stress that suppresses or dysregulates immune function, acute stress can be immunoenhancing. Acute stress enhances dendritic cell, neutrophil, macrophage, and lymphocyte trafficking, maturation, and functionandhasbeenshowntoaugmentinnateandadaptiveimmuneresponses.Acutestressexperiencedpriortonovelantigen exposureenhancesinnateimmunityandmemoryT-cellformationandresultsinasignificantandlong-lastingimmunoenhancement. Acutestressexperiencedduringantigenreexposureenhancessecondary/adaptiveimmuneresponses.Therefore,dependingonthe conditions of immune activation and the immunizing antigen, acute stress may enhance the acquisition and expression of immunoprotection or immunopathology. In contrast, chronic stress dysregulates innate and adaptive immune responses by changingthetype1–type2cytokinebalanceandsuppressesimmunitybydecreasingleukocytenumbers,trafficking,andfunction. Chronicstress also increases susceptibility to skin cancerby suppressingtype1 cytokinesand protective T cellswhile increasing suppressor T-cell function. We have suggested that the adaptive purpose of a physiologic stress response may be to promote survival,withstresshormonesandneurotransmittersservingasbeaconsthatpreparetheimmunesystemforpotentialchallenges (eg, wounding or infection) perceived by the brain (eg, detection of an attacker). However, this system may exacerbate immunopathology if the enhanced immune response is directed against innocuous or self-