Effects of cilomilast on dendritic cell function in contact sensitivity and dendritic cell migration through skin.
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.
Bäumer
Wolfgang
W
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Buenteweg 17, D-30559 Hannover, Germany. wolfgang.baeumer@tiho-hannover.de
Tschernig
Thomas
T
Sülzle
Boris
B
Seegers
Ulrike
U
Lührmann
Anke
A
Kietzmann
Manfred
M
D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002264:Carboxylic Acids; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D003509:Cyclohexanecarboxylic Acids; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009570:Nitriles; D012867:Skin / Q000187:drug effects* / Q000473:pathology
D001993:Bronchodilator Agents; D002264:Carboxylic Acids; D003509:Cyclohexanecarboxylic Acids; D009570:Nitriles; C433247:Cilomilast