UV-irradiated epidermal cells produce a specific inhibitor of interleukin 1 activity.

UV irradiation of epidermal cells (EC) in vitro and in vivo leads to an enhanced synthesis of the immunostimulating cytokine interleukin 1 (IL 1). However, UV exposure in vivo also results in local as well as systemic immunosuppression. Therefore, it was tested whether UV-exposed murine EC in culture in addition to IL 1 release an inhibitor of IL 1 activity. Supernatants of UV-irradiated BALB/c EC and of a transformed keratinocyte cell line (Pam 212) were evaluated for their ability to suppress IL 1-mediated thymocyte proliferation. Crude supernatants derived from either UV-exposed or unirradiated EC did not interfere with IL 1 activity. When supernatants were subjected to HPLC gel filtration, fractions eluting at approximately 40 kD significantly blocked the activity of EC-derived IL 1 and murine recombinant IL 1. The release of this inhibitory cytokine (EC-derived contra-IL 1 [EC-contra-IL 1]) was confined to UV-exposed BALB/c or Pam 212 keratinocytes, since no inhibitory activity was detected in supernatants of unirradiated cells. EC-contra-IL 1 also blocked IL 1-induced fibroblast proliferation but did not suppress IL 2 or IL 3 activity. Moreover, EC-contra-IL 1 did not inhibit spontaneous proliferation of a variety of cell lines (Pam 212, P388D1, L 929, EL 4). With the use of chromatofocusing EC-contra-IL 1 exhibited a pI of 8.8, and upon reversed-phase chromatography it eluted within three distinct peaks. Therefore, murine UV-exposed EC, in addition to the production of immunoenhancing cytokines, also may release immunosuppressing mediators and thereby participate in UV-induced immunosuppression. These findings further support the notion that the epidermis may not only be considered as a simple barrier against harmful agents but represents an active element of the immune system.