Inhibition by dexamethasone of Langerhans cell migration: influence of epidermal cytokine signals.
The influence of dexamethasone (DEX), a synthetic glucocorticoid, on the induction in mice of Langerhans cell (LC) migration has been investigated. Systemic treatment of mice with DEX was found to inhibit significantly the ability of a topically applied contact allergen (oxazolone) to induce the migration of LC from the epidermis and their subsequent accumulation as dendritic cells (DC) in draining lymph nodes. The stimulation of LC migration during skin sensitization is dependent upon signals provided by the epidermal cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta). It was found that treatment with DEX was unable to inhibit either LC migration or DC accumulation induced by the intradermal injection of TNF-alpha. In contrast, LC migration provoked by similar exposure of mice to IL-1beta (the action of which is dependent upon the de novo synthesis of TNF-alpha) was inhibited by DEX as was the arrival of DC in draining lymph nodes induced by this cytokine. Taken together, the data reported here indicate that DEX is able to inhibit very markedly the stimulation of LC migration during skin sensitization and it is proposed that such inhibition may represent an important aspect of the immunosuppressive properties of glucocorticoids and of their proven utility in the treatment of cutaneous inflammatory disorders. The results also indicate that DEX does not inhibit LC migration secondary to direct effects on cell motility. The proposal is that impaired LC migration results from the regulation by DEX of the de novo synthesis and/or release of TNF-alpha, an inducible epidermal cytokine that provides one important signal for LC to traffic from the skin.
Cumberbatch
M
M
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK. marie.cumberbatch@ctl.zeneca.com
Dearman
R J
RJ
Kimber
I
I
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000502:physiology; D012867:Skin / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone