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HeJ Mice and DEBR Rats Can be Reversed Using Topical Diphencyprone
Alopecia Areata-Like Hair Loss in C3H/HeJ Mice and DEBR Rats Can be Reversed Using Topical Diphencyprone Jerry Shapiro, John P. Sundberg,* Robert Bissonnette, Kevin J. McElwee,* David I. McLean, Joseph M. Carroll,³ Roy F. Oliver,² Liren Tang, and Harvey Lui
Division of Dermatology, University of British Columbia, Vancouver, British Columbia, Canada; *The Jackson Laboratory, Bar Harbor, Maine, U.S.A.; ²Department of Biologic Sciences, University of Dundee, Dundee, Scotland; ³The Genetics Institute, Andover, Maine, U.S.A.
This study demonstrates the ability to treat successfully alopecia areata-like hair loss in both mouse and rat models using topical immunotherapy with
diphencyprone. Key words: alopecia areata/animal models/topical immunotherapy. Journal of Investigative Dermatology Symposium Proceedings 4:239, 1999
T
grew hair in any animals. Mice that regrew hair showed intrafollicular CD4+ and CD8+ T lymphocytes prior to regrowth. Successful treatment was associated with a reduction of the peribulbar lymphocytic in®ltrate and development of in¯ammation in the upper dermis. In rats there was a paucity of lymphocytic in®ltrate on both the untreated and the treated side and thus no shifts of lymphocytes were apparent. This study demonstrates the ability to successfully treat AA-like hair loss in both mouse and rat models using DPCP. In the C3H/ HeJ alopecia areata mouse model, regrowth with DPCP is correlated with a depletion of peribulbar lymphocytes.
opical immunotherapy with diphencyprone has become the treatment of choice for most adult patients with chronic severe alopecia areata (AA) (Shapiro and Price, 1998). The mechanism of action is unknown. The side-effect pro®le is signi®cant with eczema, lymphadenopathy, and pigment changes. There are likely key reactions that account for most of the bene®cial effect of diphencyprone (DPCP). Animal models for alopecia areata may allow us to understand and dissect out the sequence of immunologic events that occur during topical immunotherapy. The two currently available animal models for alopecia areata, the C3H/HeJ mouse (Sundberg et al, 1994; McElwee et al, 1998) and the DEBR rat (Michie et al, 1991, Zhang and Oliver, 1994) were treated unilaterally on a weeky basis with DPCP for 16 wk. The contralateral sides of each animal were treated only with vehicle. Eighteen mice and 10 rats were studied. Two mice were sacri®ced at the beginning of the study to serve as baseline controls. Two additional mice were necropsied prior to hair regrowth at weeks 3 and 7. The remaining 14 mice were necropsied at the end of the study. All 10 rats were necropsied at the end of the study. Immunophenotypic analysis for T cell populations were performed. Nine out of 14 mice and 10 of 10 rats regrew hair unilaterally on the DPCP-treated sides. None of the contralateral untreated sides
REFERENCES McElwee KJ, Boggess D, Olivry T, et al: Comparison of alopecia areata in human and non-human mammalian species. Pathobiology 66:90±107, 1998 Michie H, Jahoda C, Oliver R, Johnson B: The DEBR rat: an animal model of human alopecia areata. Br J Dermatol 125:94±100, 1991 Shapiro J, Price VH: Hair regrowth, Therapeutic agents. Dermatol Clin 16:341±356, 1998 Sundberg J, Cordy W, King L: Alopecia areata in aging C3H/HeJ mice. J Invest Dermatol 102:847±856, 1994 Zhang J, Oliver R: Immunohistological study of the development of the cellular in¯iltrate in the pelage follicles of the DEBR model for alopecia areata. Br J Dermatol 130:405±414, 1994
Manuscript received January 11, 1999; revised February 11, 1999; accepted for publication February 25, 1999. Reprint requests to: Dr. Jerry Shapiro, University of British Columbia, Division of Dermatology, Skin Care Center, 835 West Tenth Avenue, Vancouver, BC, Canada V5Z4E8. 1087-0024/99/$14.00
´ Copyright # 1999 by The Society for Investigative Dermatology, Inc. 239
Division of Dermatology, University of British Columbia, Vancouver, British Columbia, Canada; *The Jackson Laboratory, Bar Harbor, Maine, U.S.A.; ²Department of Biologic Sciences, University of Dundee, Dundee, Scotland; ³The Genetics Institute, Andover, Maine, U.S.A.
This study demonstrates the ability to treat successfully alopecia areata-like hair loss in both mouse and rat models using topical immunotherapy with
diphencyprone. Key words: alopecia areata/animal models/topical immunotherapy. Journal of Investigative Dermatology Symposium Proceedings 4:239, 1999
T
grew hair in any animals. Mice that regrew hair showed intrafollicular CD4+ and CD8+ T lymphocytes prior to regrowth. Successful treatment was associated with a reduction of the peribulbar lymphocytic in®ltrate and development of in¯ammation in the upper dermis. In rats there was a paucity of lymphocytic in®ltrate on both the untreated and the treated side and thus no shifts of lymphocytes were apparent. This study demonstrates the ability to successfully treat AA-like hair loss in both mouse and rat models using DPCP. In the C3H/ HeJ alopecia areata mouse model, regrowth with DPCP is correlated with a depletion of peribulbar lymphocytes.
opical immunotherapy with diphencyprone has become the treatment of choice for most adult patients with chronic severe alopecia areata (AA) (Shapiro and Price, 1998). The mechanism of action is unknown. The side-effect pro®le is signi®cant with eczema, lymphadenopathy, and pigment changes. There are likely key reactions that account for most of the bene®cial effect of diphencyprone (DPCP). Animal models for alopecia areata may allow us to understand and dissect out the sequence of immunologic events that occur during topical immunotherapy. The two currently available animal models for alopecia areata, the C3H/HeJ mouse (Sundberg et al, 1994; McElwee et al, 1998) and the DEBR rat (Michie et al, 1991, Zhang and Oliver, 1994) were treated unilaterally on a weeky basis with DPCP for 16 wk. The contralateral sides of each animal were treated only with vehicle. Eighteen mice and 10 rats were studied. Two mice were sacri®ced at the beginning of the study to serve as baseline controls. Two additional mice were necropsied prior to hair regrowth at weeks 3 and 7. The remaining 14 mice were necropsied at the end of the study. All 10 rats were necropsied at the end of the study. Immunophenotypic analysis for T cell populations were performed. Nine out of 14 mice and 10 of 10 rats regrew hair unilaterally on the DPCP-treated sides. None of the contralateral untreated sides
REFERENCES McElwee KJ, Boggess D, Olivry T, et al: Comparison of alopecia areata in human and non-human mammalian species. Pathobiology 66:90±107, 1998 Michie H, Jahoda C, Oliver R, Johnson B: The DEBR rat: an animal model of human alopecia areata. Br J Dermatol 125:94±100, 1991 Shapiro J, Price VH: Hair regrowth, Therapeutic agents. Dermatol Clin 16:341±356, 1998 Sundberg J, Cordy W, King L: Alopecia areata in aging C3H/HeJ mice. J Invest Dermatol 102:847±856, 1994 Zhang J, Oliver R: Immunohistological study of the development of the cellular in¯iltrate in the pelage follicles of the DEBR model for alopecia areata. Br J Dermatol 130:405±414, 1994
Manuscript received January 11, 1999; revised February 11, 1999; accepted for publication February 25, 1999. Reprint requests to: Dr. Jerry Shapiro, University of British Columbia, Division of Dermatology, Skin Care Center, 835 West Tenth Avenue, Vancouver, BC, Canada V5Z4E8. 1087-0024/99/$14.00
´ Copyright # 1999 by The Society for Investigative Dermatology, Inc. 239