Epidermal keratinocyte production of interferon-gamma immunoreactive protein and mRNA is an early event in allergic contact dermatitis

Previous work has indicated the importance of cytokine cascades in the induction of contact dermatitis, but there is little information on the cellular localization of cytokines in human skin, particularly during the early phases of the inflammatory response to contact allergens. Using in situ hybridization for mRNA and immunocytochemistry on biopsies from a series of 16 patients with known allergic contact dermatitis, we examined the kinetics of early cytokine production after challenge with relevant or irrelevant antigen, We show that epidermal keratinocytes from patients challenged in vivo with allergen, but not irrelevant antigen, rapidly synthesize (within 4 h) mRNA for interferon-gamma and produce immunoreactive interferon-gamma, Interleukin-1 alpha and interleukin-8 mRNA were also detected but showed no correlation with relevant antigen challenge. This study demonstrates that keratinocytes can produce interferon-gamma and that this production is linked to challenge with relevant antigen in allergic contact dermatitis. These findings indicate that keratinocytes may amplify allergen-specific T-lymphocyte-triggered interferon-gamma-dependent responses and might partially explain the speed of reaction in this common disease and other delayed hypersensitivity reactions involving the skin.