Stress-induced augmentation of immune function - The role of stress hormones, leukocyte trafficking, and cytokines

Delayed-type hypersensitivity (DTH) reactions represent cell-mediated immune responses that exert important immunoprotective (resistance to viruses. bacteria and fungi) or immunopathological (allergic or autoimmune hypersensitivity) effects. We initially utilized he skin DTH response as an experimental in vivo model to study neuro endocrine-immune interactions in rodents. We hypothesized that just as an acute stress response prepares the cardiovascular and musculoskeletal systems for fight or flight, it may also prepare the immune system for challenges which may be imposed by a stressor. The skin DTH model allowed us to examine the effects of stress at the time of primary and secondary exposure to antigen. Studies showed that acute (2 h) stress experienced before primary or secondary antigen exposure induces a significant enhancement of skin DTH. Importantly. this enhancement involved innate as well as adaptive immune mechanisms. Adrenalectomy eliminated the stress induced enhancement of DTH. Acute administration of physiological (stress) concentrations of corticoserone and/or epinephrine to adrenalectomized animals enhanced skin DTH. Compared with controls. DTH sites from acutely stressed or hormone-injected animals showed significantly greater erythema and enduration, numbers of infiltrating leukocytes, and levels of cytokine gene expression, In contrast to acute stress. chronic stress was immunosuppressive. Chronic exposure to corticosterone. or acute exposure to dexamethasone significantly suppressed skin DTH, These results Suggest that during acute stress. endogenous stress hormones enhance skin immunity by increasing leukocyte trafficking and cytokine gene expression at the site of antigen entry. While these results are discussed from a mechanistic and clinical relevance perspective. it is acknowledged that much work remains to be done to elucidate the precise mechanisms mediating these bi-directional effects of stress and stress hormones and their clinical ramifications. (C) 2002 Elsevier Science (USA). All rights reserved.