Interleukin-la mediates phorbol ester-induced inflammation

The topical application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to murine skin produces acute inflammatory and hyperplastic responses that have been associated with the promotion stage of skin carcinogenesis. It has been shown in a previous study that TPA induces the expression of the highly inflammatory cytokine, interleukin (IL) -la, in the epidermis of SENCAR mice. The goal of this study was to investigate the role of IL-la in several TPAinduced responses in skin. Topical application of TPA (1 gig) enhanced the production of immunoreactive IL-la protein, primarily associated with the suprabasal keratinocytes. IL-la intradermally injected in the dorsal surface significantly increased (P < 0.001) vascular permeability at low concentrations (1-1000 tU) and increased (P < 0.001) inflammatory cell infiltration and epidermal hyperplasia at higher concentrations (103 U). TPA produced fourfold increases in vascular permeability as measured by Evans blue dye leakage; this effect was prevented by intradermal injection of anti-IL-la antibody (2575 gig). Furthermore, injected anti-IL-la antibody significantly reduced (P < 0.001) TPA-induced inflammatory cell infiltration and epidermal hyperplasia. This study suggests that IL-la directly or indirectly mediates the inflammatory and hyperplastic responses elicited by topical treatment with TPA.-Lee, W. Y., Lockniskar, M. F., Fischer, S. M. Interleukin-la mediates phorbol ester-induced inflammation and epidermal hyperplasia. FASEBJ. 8: 1081-1087; 1994.