Production and in situ localization of cutaneous tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) following skin sensitization

The induction of contact sensitization and other cutaneous immune responses is dependent upon the activity of epidermal cytokines. One such, keratinocyte-derived tumour necrosis factor α (TNF-α), is thought to provide the stimulus for the migration of Langerhans cells from the epidermis and their accumulation as immunocompetent dendritic cells in draining lymph nodes. In these investigations we have examined the stimulation by allergen of cutaneous TNF-α production and the induced epidermal expression of mRNA for TNF-α. Topical exposure of mice to oxazolone, a skin-sensitizing chemical, resulted in cutaneous TNF-α protein production that was maximal 2-h following treatment and then declined markedly. The same treatment resulted in highly localized and transient expression of epidermal TNF-α mRNA as judged by in situ hybridization. Epidermal mRNA for TNF-α was apparent 10 min following exposure to oxazolone, but was no longer detectable at 20 min. A similar pattern of TNF-α mRNA expression in the epidermis was provoked by intradermal exposure to interleukin 1β, a cytokine shown previously to induce TNF-α. Such rigorous regulation of temporal and spatial expression was shown not to be a characteristic of all epidermal cytokines induced by chemical allergen. Exposure to oxazolone under the same conditions resulted in a more widespread and more persistent expression of epidermal mRNA for interleukin 6. These data demonstrate that during skin sensitization the induced expression of epidermal TNF-α is finely controlled in space and time. It is proposed that such regulation facilitates the initiation of cutaneous immune responses while preventing excessive inflammation that would result from more persistent TNF-α production.