The effect of the PDE-4 inhibitor (cipamfylline) in two human models of irritant contact dermatitis.
BACKGROUND
New therapeutic approaches have to be considered in the treatment of irritant contact dermatitis (ICD). Recently, phosphodiesterase 4 (PDE-4) inhibitors have been introduced as nonsteroidal, antiinflammatory agents. These agents inhibit the secretion of the cytokines thought to be involved in the pathogenesis of ICD. We investigated the effect of a new selective PDE-4 inhibitor (cipamfylline) in human models using single and repeated exposures to an irritant in a blind, randomized pilot study with healthy volunteers. We compared the effect of cipamfylline ointment with a strong corticosteroid (betamethasone-17-valerate) and with a placebo ointment.


METHODS
Ten volunteers were patch tested at four investigation sites with sodium dodecyl sulphate (1%) for 24 h. In a model that simulates chronic damage, 11 volunteers were patch tested with sodium dodecyl sulphate (0.2%) for 4 h daily for four consecutive days. The investigation sites were treated once a day with the above-mentioned agents. One site was left untreated. We used erythema scoring, measurements of transepidermal water loss (TEWL) and several immunohistochemical markers for epidermal proliferation and differentiation.


RESULTS
Repeated application revealed that betamethasone-17-valerate caused a statistically significant reduction in erythema and TEWL compared to cipamfylline and placebo. We also observed a significant suppression of proliferating cells and cytokeratin 16 expression at sites treated with betamethasone compared to the other sites. In the model for acute ICD, no significant differences were seen between the investigated sites.


CONCLUSIONS
Our results show that betamethasone-17-valerate may modulate the response in ICD. In this human model of ICD we could not confirm the efficacy of cipamfylline. Clinical studies are needed before the effect of PDE-4 inhibitors in ICD can be refuted with certainty.
Kucharekova
M
M
Department of Dermatology, University Medical Centre St Radboud, P.O. Box 9101, Nijmegen, The Netherlands. m.kucharekova@derma.umcn.nl
Hornix
M
M
Ashikaga
T
T
T'kint
S
S
de Jongh
G J
GJ
Schalkwijk
J
J
van de Kerkhof
P C M
PC
van der Valk
P G M
PG
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000328:Adult; D000368:Aged; D001624:Betamethasone Valerate / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D017453:Dermatitis, Irritant / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004890:Erythema / Q000209:etiology / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007633:Keratins / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage; D013501:Surface-Active Agents / Q000008:administration & dosage; D014870:Water Loss, Insensible / Q000187:drug effects; D014970:Xanthines / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D013501:Surface-Active Agents; D014970:Xanthines; D012967:Sodium Dodecyl Sulfate; D007633:Keratins; D001624:Betamethasone Valerate; C466758:cipamfylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4