Successful treatment of alopecia areata-like hair loss with the contact sensitizer squaric acid dibutylester (SADBE) in C3H/HeJ mice.
A type of hair loss closely resembling human alopecia areata has been described in C3H/HeJ mice. In order to test the assumed analogy with human alopecia areata, we investigated the efficacy of treatment with the contact allergen squaric acid dibutylester. In 12 C3H/HeJ mice with alopecia areata an allergic contact dermatitis was induced and elicited weekly on one side of the back by topical applications of squaric acid dibutylester. Overt hair regrowth was observed only on the treated side of the back in nine of 12 mice. Histopathologic examination revealed a change in the distribution of the inflammatory infiltrate from a dense perifollicular lymphocytic infiltrate around the mid and lower regions of hair follicles in untreated skin to a uniform presence in the upper dermis in treated skin. Immunohistomorphometric studies revealed that treatment with squaric acid dibutylester increased the CD4+/CD8+ ratio from approximately 1:2 in untreated alopecia areata to 1:1 in treated alopecia areata. Additional immunohistochemical investigations showed an aberrant expression of major histocompatibility complex class I, major histocompatibility complex class II and intercellular adhesion molecule 1 on keratinocytes of the mid and lower parts of hair follicles in untreated alopecia areata. In successfully treated skin ectopic major histocompatibility complex class I and II expression was clearly reduced, whereas intercellular adhesion molecule 1 expression showed only minor changes. In conclusion, alopecia areata-like hair loss in C3H/HeJ mice responded to treatment with the contact sensitizer squaric acid dibutylester analogous to human alopecia areata. Moreover, successful treatment changes the aberrant expression of major histocompatibility complex class I and II in a way similar to that observed in human alopecia areata. These observations support the concept that alopecia areata-like hair loss in C3H/HeJ mice can be utilized as an appropriate model for the study of human alopecia areata.
Freyschmidt-Paul
P
P
Department of Dermatology, Philipp University, Marburg, Germany.
Sundberg
J P
JP
Happle
R
R
McElwee
K J
KJ
Metz
S
S
Boggess
D
D
Hoffmann
R
R
D000485:Allergens / Q000627:therapeutic use*; D000506:Alopecia Areata / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016516:CD4-CD8 Ratio / Q000187:drug effects; D003503:Cyclobutanes / Q000627:therapeutic use*; D020405:Dermis / Q000187:drug effects / Q000473:pathology; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects; D005260:Female; D006197:Hair / Q000187:drug effects / Q000254:growth & development; D018859:Hair Follicle / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012627:Sebaceous Glands / Q000737:chemistry / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
D000485:Allergens; D003503:Cyclobutanes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1; C020637:squaric acid dibutyl ester