Effects of cilomilast on dendritic cell function in contact sensitivity and dendritic cell migration through skin

Abstract

The phosphodiesterase 4 inhibitor cilomilast demonstrated strong inhibitory effects in a model of allergic contact dermatitis. In this study, we examined whether this inhibitory effect is at least partly due to modulation of dendritic cell function. Bone marrow-derived dendritic cells were pulsed with the sensitizer toluene-2,4-diisocyanate and administered subcutaneously to nonsensitized mice. Five days later, the mice were challenged with a low dose of toluene-2,4-diisocyanate onto the ears. In contrast to sham-treated mice, mice obtaining toluene-2,4-diisocyanate pulsed dendritic cells showed a significant increase in ear swelling. This swelling was not influenced when the dendritic cells were pre-incubated with cilomilast. When cilomilast was administered systemically simultaneously to the application of toluene-2,4-diisocyanate pulsed cells, there was an impaired allergic reaction provoked 5 days later. Additionally, a topical treatment with cilomilast resulted in a significant inhibition of skin dendritic cell migration. These results indicate that the antigen-presenting function of dendritic cells is not influenced by cilomilast but the dendritic cell T cell interaction and dendritic cell migration is modulated.