Induction and localization of cutaneous interleukin-1 beta mRNA during contact sensitization

Chemical allergens that induce contact sensitivity cause changes in levels of epidermal cytokines, In mice one of the earliest epidermal cytokines to be upregulated following sensitization is interleukin-1 beta (IL-1 beta), T he present study investigated the kinetics and in situ localization of indu ced IL-1 beta expression in mouse skin following topical exposure to the co ntact allergen oxazolone. Mice were exposed topically to 1% oxazolone, with control mice exposed to vehicle (acetone:olive oil 4:1) alone, and at vari ous times thereafter skin was excised for IL-1 beta mRNA and protein determ ination by in situ hybridization and enzyme-linked immunosorbant assay (ELI SA), respectively. IL-1 beta mRNA was found to be expressed constitutively at low levels in skin from naive (untreated) and vehicle-treated mice, with mRNA localized in some hair follicles and sebaceous glands; no IL-1 beta m RNA was detected in the epidermis of control animals. Following topical exp osure of mice to oxazolone for 5-15 min, upregulation of IL-1 beta mRNA was observed in the epidermis, dermis, hair follicles, and sebaceous glands; a t 90 min and beyond the pattern of IL-1 beta mRNA expression declined towar d control. Analysis of whole skin homogenates by ELISA demonstrated cutaneo us IL-1 beta protein to be present constitutively in both vehicle-treated a nd naive mice. Following exposure to oxazolone, cutaneous IL-1 beta protein expression was elevated at 30 min, decreased at 1 h, and fell below the li mit of detection of the assay at 2 h before returning to constitutive level s at 4 and 24 h. IL-1 beta protein levels in vehicle-treated mice, naive mi ce, and mice treated with the respiratory allergen trimellitic anhydride we re unchanged over this time period. The present study demonstrated that IL- 1 beta mRNA expression was upregulated rapidly and transiently in well-defi ned regions of mouse epidermis and dermis during contact sensitization, and was succeeded by an elevation in IL-1 beta protein. This early highly loca lized upregulation of IL-1 beta lends further support to the hypothesis tha t this cytokine plays a key role in the initial stages of skin sensitizatio n. Such information will enhance our understanding of the molecular process es involved in allergic contact dermatitis and may provide a mechanistic ba sis for designing refined animal and in vitro alternatives to existing mode ls of skin sensitization, (C) 2000 Academic Press.