title: Topical application of dithranol on normal skin induces epidermal hyperproliferation and increased Ks8.12 binding.
abstract: Although dithranol has been used for 75 years in the treatment of psoriasis, its working mechanism is still not resolved. In order to further define the mode of action of dithranol, the interference with normal skin was studied. The effect of dithranol on epidermal proliferation, keratinization and inflammation was examined using immunohistochemistry. Punch biopsies from 6 volunteers who applied dithranol 0.5% in petrolatum were taken before application, after 48 and 96 h. Biopsies were processed for assessing epidermal proliferation by Ki67 binding (cycling cells), for keratinization by Ks8.12 binding (keratin 13 and 16, keratin 16 is expressed by hyperproliferative keratinocytes) and RKSE60 binding (keratin 10). For assessing inflammation the antibodies antielastase (polymorphonuclear leukocytes (PMN)), T11 (T lymphocytes, CD2), T6 (Langerhans cells, CD1a) and WT14 (monocytes/macrophages, CD14) were used. Ki-67 staining started to increase between 48 and 96 h whereas Ks8.12 binding had increased already between 0 and 48 h. RKSE60 staining showed a decline between 48 and 96 h. Inflammation in the dermis showed an increase after 48 h, and continued to increase. In the inflammatory infiltrate, the accumulation of PMN was limited compared to the pronounced infiltration of T lymphocytes. Langerhans cell shape and epidermal position altered in 4 volunteers. Application of dithranol on normal skin produces analogies and discrepancies compared to application of dithranol on psoriatic lesions. Direct interference with epidermal growth and differentiation seems less likely as the antipsoriatic principle.
authors.affiliation: Department of Dermatology, University Hospital Nijmegen, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: de Zwart
authors.forename: E M
authors.initials: EM
authors.lastname: de Jong
authors.forename: P C
authors.initials: PC
authors.lastname: van de Kerkhof
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000875:Anthralin / Q000008:administration & dosage* / Q000494:pharmacology; D000906:Antibodies / Q000008:administration & dosage; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism*; D008297:Male
chemical_list: D000906:Antibodies; D007633:Keratins; D000875:Anthralin