Autoradiographic in vitro-examination of psoriatic skin before, during and after dithranol treatment

Steigleder, G. K.; Schumann, Hauke; Lennartz, K. J.

doi:10.1007/bf00595423

Cited by 42 publications

(7 citation statements)

References 20 publications

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“…An attractive explanation for this obser vation is provided by the fact that dithranol inhibits DNA replication [17,18] and arrests cells in the S phase. This results in a de creased thymidine uptake as reported in the literature [19,20] and an unchanged number of cells in the S phase as observed in the present study. The discrepancy between per sistent hyperproliferation and decreased ker atin 16 expression following treatment with dithranol suggests that the expression of this keratin is not directly linked with hyperpro liferation, but is rather a marker for a more general disturbance of epidermal integrity.…”

Section: Discussionsupporting

confidence: 78%

The Relevance of Salicylic Acid in the Treatment of Plaque Psoriasis with Dithranol Creams

Mare

Calis

Hartog

et al. 1988

Skin Pharmacol Physiol

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The relevance of salicylic acid in dithranol creams was evaluated in a double-blind study. Patients with chronic plaque psoriasis were treated using a short-contact schedule for dithranol on an outpatient basis. A left-right comparison was carried out between sites treated with either dithranol with 2 % salicylic acid (D+S) or dithranol in the same base without salicylic acid (D-S). Clinical results were evaluated once a week using the psoriasis area severity index. In order to quantify the improvement, flow cytometric measurements were done using the monoclonal antibody K_s8.12, recognizing keratin 16 in normal and lesional epidermis. Simultaneously, relative DNA content was quantified which previously was described as a useful method to monitor a therapeutic effect. Both PASI scores and K_s8.12 binding decreased after 6 weeks treatment with D+S and D-S. However, percentages of cells in SG₂M phases did not show a significant change. No significant difference was observed between sites treated with either D+S or D-S. Therefore we conclude that the addition of salicylic acid in a concentration of 2 % does not enhance the efficacy of dithranol creams and we confirm that K_s8.12 is a useful quantitative marker for therapeutic efficacy.

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Section: Discussionsupporting

confidence: 78%

The Relevance of Salicylic Acid in the Treatment of Plaque Psoriasis with Dithranol Creams

Mare

Calis

Hartog

et al. 1988

Skin Pharmacol Physiol

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“…With deriv. 4 we found an identical decrease of cell growth and a reduced cytotoxicity in comparison to anthralin. For deriv.…”

Section: Influence Ofc-2 Substitutionsupporting

confidence: 74%

“…Among the anthralin derivatives tested we found seven compounds (deriv. 4,6,8,9,10,11,12) exerting cell growth inhibitory and cytotoxic effects approximating or exceeding those of anthralin. For future investigations these substances would be of special interest as hydrophilic anthralin model compounds and antipsoriatic drugs.…”

Section: Resultsmentioning

confidence: 99%

Structure‐function relationship of new anthralin derivatives assayed for growth inhibition and cytotoxicity in human keratinocyte cultures

Bonnekoh

Tanzer

Seidel

et al. 1991

Archiv der Pharmazie

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HaCaT keratinocyte cultures were exposed to twelve hydrophilic anthralin derivatives 1 to 12 with substituents at C-l and C-8 of the anthrone skeleton, of one H at C-10 and of both H's at C-10 by lacton rings ( fig. 1). After 3 uM treatment growth was determined by cellular protein content, ^-thymidineand 14 C-amino-acid-uptake and cytotoxicity by the release of cytoplasmic LDH into the culture medium.-In comparison to acetone control (100%) anthralin suppressed mean protein content, as well as DNA-and protein-synthesis to 33, 28, and 21%, respectively, and the drug revealed an enzyme release of 660%. In relation to the parent drug we found similar cell growth inhibitory effects of compounds 4, 6, 8, 9, 10, and 12. Deriv. 4, 8, and 10 were, however, to some extent less cytotoxic than anthralin, whereas deriv. 6, 9, and 12 were in the same range. An extreme suppression of growth parameters which differed from the anthralin effect by a factor 0.5-0.8 was caused by deriv. 11, showing the same cytotoxicity. Deriv. 1, 2, 3,5, and 7 did not demonstrate any cytotoxicity. Concerning growth parameters, deriv. 2 induced a slight stimulation, deriv. 3 and 7 were completely ineffective, deriv. 1 and 5 induced slightly to moderately inhibited proliferation but both being much less effective than anthralin. These data indicate that the "minimum structure" concept by Krebs and Schaltegger -claiming l-hydroxy-9-anthrone as a precondition for clinical antipsoriatic potency -is not valid at least in cell-biological tests and point toward possible usefulness of some experimental model compounds as alternative antipsoriatics.

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“…In previous studies, a decrease in 3[H]-thymidine incorporation, a decrease in DNA content and cells in the SG2M phase, and a decrease in cells staining with the antibody Ki-67 have been observed during treatment of psoriatic lesions with di thranol [5,9,15,16]. Also keratinocytes in culture showed a decrease in growth after incubation with dithranol [17], In the present study, normal skin in vivo showed a hyperproliferative response to dithranol applica tions, as demonstrated by an increase of Ki-67-stained nuclei.…”

Section: Discussionmentioning

confidence: 99%

“…The antipsoriatic principle, so far, is not exactly downregulation of epidermal proliferation and a decrease of inflammatory cells in the dermis [5][6][7][8][9]. In contrast, dithranol induces erythema in the surrounding skin of a pso riatic lesion [ 10].…”

Section: Introductionmentioning

confidence: 99%

Topical Application of Dithranol on Normal Skin Induces Epidermal Hyperproliferation and Increased Ks8.12 Binding

Zwart

Jong²,

Kerkhof³

1992

Skin Pharmacol Physiol

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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, CD 14) were used. Ki-67 staining started to increase between 48 and 96h 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.

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Autoradiographic in vitro-examination of psoriatic skin before, during and after dithranol treatment

Cited by 42 publications

References 20 publications

The Relevance of Salicylic Acid in the Treatment of Plaque Psoriasis with Dithranol Creams

The Relevance of Salicylic Acid in the Treatment of Plaque Psoriasis with Dithranol Creams

Structure‐function relationship of new anthralin derivatives assayed for growth inhibition and cytotoxicity in human keratinocyte cultures

Topical Application of Dithranol on Normal Skin Induces Epidermal Hyperproliferation and Increased Ks8.12 Binding

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