Stress-induced enhancement of skin immune function: A role for γ interferon

Firdaus S. Dhabhar, Abhay R. Satoskar, Horst Bluethmann, John R. David, Bruce S. McEwen

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129 Scopus citations


Contrary to the widespread belief that stress is necessarily immunosuppressive, recent studies have shown that, under certain conditions, stress can induce a significant enhancement of a skin cell-mediated immune response [delayed-type hypersensitivity (DTH) or contact hypersensitivity]. Adrenal stress hormones and a stress-induced trafficking of leukocytes from the blood to the skin have been identified as systemic mediators of this immunoenhancement. Because y interferon (IFNγ) is an important cytokine mediator of DTH, the studies described here were designed to examine its role as a local mediator of the stress-induced enhancement of skin DTH. The effect of acute stress on skin DTH was examined in wild-type and IFNγ receptor- deficient (IFNγR-/-) mice that had previously been sensitized with 2,4- dinitro-1-fluorobenzene. Acutely stressed wild-type mice showed a significantly larger DTH response than nonstressed mice. In contrast, IFNγR- /- mice failed to show a stress-induced enhancement of skin DTH. Immunoneutralization of IFNγ in wild-type mice significantly reduced the stress-induced enhancement of skin DTH. In addition, an inflammatory response induced by direct IFNγ administration to the skin was significantly enhanced by acute stress. Our results suggest that IFNγ is an important local mediator of a stress-induced enhancement of skin DTH. These studies are clinically relevant because, depending on the nature of the antigen, DTH reactions mediate numerous protective (e.g., resistance to viral, bacterial, parasitic, and fungal infections) or pathological (e.g., autoimmune reactions and contact sensitivity reactions such as that to poison ivy) immune responses.

Original languageEnglish (US)
Pages (from-to)2846-2851
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number6
StatePublished - Mar 14 2000
Externally publishedYes

ASJC Scopus subject areas

  • General


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