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

Contrary to the widespread belief that stress is necessarily immunosuppress ive, recent studies have shown that, under certain conditions, stress can i nduce a significant enhancement of a skin cell-mediated immune response [de layed-type hypersensitivity (DTH) or contact hypersensitivity]. Adrenal str ess hormones and a stress-induced trafficking of leukocytes from the blood to the skin have been identified as systemic mediators of this immunoenhanc ement. Because gamma interferon (IFN gamma) is an important cytokine mediat or 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 IFN gamma recepto r-deficient (IFN gamma R-/-) mice that had previously been sensitized with 2,4-dinitro-1-fluorobenzene. Acutely stressed wild-type mice showed a signi ficantly larger DTH response than nonstressed mice. In contrast, IFN gamma R-/- mice failed to show a stress-induced enhancement of skin DTH, Immunone utralization of IFN gamma in wild-type mice significantly reduced the stres s-induced enhancement of skin DM. In addition, an inflammatory response ind uced by direct IFN gamma administration to the skin was significantly enhan ced by acute stress. Our results suggest that IFN gamma is an important loc al mediator of a stress-induced enhancement of skin DTH. These studies are clinically relevant because, depending on the nature of the antigen, DTH re actions mediate numerous protective (e.g., resistance to viral, bacterial, parasitic, and fungal infections) or pathological (e.g., autoimmune reactio ns and contact sensitivity reactions such as that to poison ivy) immune res ponses.