Therapeutic interventions in mice with chronic proliferative dermatitis (cpdm/cpdm).
Chronic proliferative dermatitis (cpd) is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm). The dermatitis is characterized by redness, hairloss, scaling, pruritus and histologically by epithelial hyperproliferation, infiltration of eosinophils, macrophages and mast cells. Lesions similar to those in the skin occur in the esophagus and forestomach. In this paper, we describe the effect of drug treatments directed against epidermal hyperproliferation (calcipotriene and etretinate), against inflammation (corticosteroids and dapsone) and against pruritus (loratidine and capsaicin). The criteria used to objectively estimate the effect of the treatment were 1) macroscopic evaluation of the lesions (cpd score), 2) degree of epithelial hyperproliferation assessed by BrdU incorporation and epithelial thickness, and 3) microscopic evaluation of the inflammatory cells in the skin samples. Treatment of the cpdm/cpdm mice with calcipotriene (5 microg/day for 3 weeks) inhibited epidermal proliferation and the number of eosinophils. Systemic etretinate treatment (30 microg/g/day for 3 weeks) was not very effective. Topical corticosteroids (0.05 microg/day, for 3 weeks) exerted a therapeutic effect on the hyperproliferation and the number of eosinophils. Oral dapsone treatment (34 microg/g/day, for 5 weeks) reduced the BrdU incorporation in the skin and the epithelial thickness in the esophagus. The anti-histamine loratidine (orally, 1.7 microg/ g/day, for 4 weeks) reduced the severity of the lesions macroscopically, probably by suppressing the pruritus. Capsaicin (topically, 30 mM, for 5 weeks) also reduced the severity of the macroscopic observable lesions. Moreover, capsaicin reduced the dorsal and ventral epidermal thickness. The results from this and previous studies indicate that steroids (topically and systemically) and less strongly calcipotriene are the most effective treatments for the lesions observed in the cpdm/cpdm mice, since both hyperproliferation and the influx of eosinophils are reduced. Although the pathogenesis of the cpd lesions remains to be determined, our results indicate that the cpdm/cpdm mouse can be used to investigate new drugs for their possible application in chronic dermatitis.
Gijbels
M J
MJ
TNO Prins Maurits Laboratory, Rijswijk, The Netherlands.
Elliott
G R
GR
HogenEsch
H
H
Zurcher
C
C
van den Hoven
A
A
Bruijnzeel
P L
PL
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000982:Antipruritics / Q000627:therapeutic use; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002211:Capsaicin / Q000627:therapeutic use; D002455:Cell Division; D002908:Chronic Disease; D003622:Dapsone / Q000627:therapeutic use; D003872:Dermatitis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D005050:Etretinate / Q000627:therapeutic use; D007641:Keratolytic Agents / Q000627:therapeutic use; D017336:Loratadine / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000982:Antipruritics; D007641:Keratolytic Agents; C055085:calcipotriene; D005050:Etretinate; D017336:Loratadine; D003622:Dapsone; D002117:Calcitriol; D002211:Capsaicin