Stress as an endogenous adjuvant: Augmentation of the immunization phase of cell-mediated immunity

Kavitha Viswanathan, Christine Daugherty, Firdaus S. Dhabhar

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


Stress is thought to be immunosuppressive but paradoxically exacerbates inflammatory and autoimmune diseases. We initially showed that acute stress enhances skin immunity. Such immunoenhancement could promote immunoprotection in case of wounding, infection or vaccination but could also exacerbate immunopathological diseases. Here we identify the molecular and cellular mediators of the immunoenhancing effects of acute stress. Compared with non-stressed mice, acutely stressed animals showed significantly greater pinna swelling and leukocyte infiltration, and up-regulated macrophage chemoattractant protein-1, macrophage inflammatory protein-3α, IL-1α, IL-1β, IL-6, tumor necrosis factor-α and IFN-γ, but not IL-4 gene expression at the site of primary antigen exposure. Stressed animals also showed enhanced maturation and trafficking of dendritic cells (DCs) from skin to lymph nodes (LNs), higher numbers of activated macrophages in skin and LNs, increased T cell activation in LNs, and enhanced recruitment of surveillance T cells to skin. These findings show that important interactive components of innate (DCs and macrophages) and adaptive (surveillance T cells) immunity are mediators of the stress-induced enhancement of a primary immune response. Such enhancement during primary immunization may induce a long-term increase in immunologic memory resulting in subsequent augmentation of the immune response during secondary antigen exposure. Thus, the evolutionarily adaptive fight-or-flight stress response may protectively prepare the immune system for impending danger (e.g. infection and wounding by a predator), but may also contribute to stress-induced exacerbation of inflammatory and autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)1059-1069
Number of pages11
JournalInternational Immunology
Issue number8
StatePublished - Aug 2005
Externally publishedYes


  • Evolution
  • Hormone
  • Langerhans cell
  • Leukocyte trafficking
  • Memory lymphocyte
  • Psychopysiological stress
  • Skin diseases
  • Surveillance
  • Survival

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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