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Effects of glucocorticosteroids on primary human skin fibroblasts

I. Inhibition of the Proliferation of Cultured Primary Human Skin and Mouse L929 Fibroblasts

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Summary

Various glucocorticosteroids were added to logarithmically growing cultures of primary human skin fibroblasts and of mouse L929 fibroblasts. These steroids inhibited proliferation of the human fibroblasts at concentrations which fall in a range expected to occur during the topical treatment of skin disorders. In terms of the concentrations required for the inhibition hydrocortisone was least and clobetasol-17-propionate most effective. All other steroids studied (hydrocortisone-17-butyrate, triamcinolone acetonide, betamethasone-17-valerate and hydrocortisone-21-acetate) showed medium effectiveness. Fluorination as such may not enhance the inhibitory effect. The inhibition was independent of the source (baby foreskin or adult arm skin) and passage number (7th to 13th or 15th and 16th passage, respectively) of the cells. The possible relationship between the inhibition of cell proliferation by such steroids and their therapeutic effect in psoriasis and their atrophic side effects is discussed.

Mouse L929 fibroblasts were affected at 103–104-fold lower steroid concentrations and the range of the effective concentrations was 104–105 times as wide as that for the primary human skin fibroblasts. It was concluded that these mouse fibroblasts are a poor model system for the study of in vivo effects of glucocorticosteroids in man.

Zusammenfassung

Eine Anzahl Glucocorticosteroide wurden logarithmisch wachsenden Kulturen primärer menschlicher Hautfibroblasten und L929 Mäuse-Fibroblasten hinzugefügt.

Im Konzentrationsbereich, der während der lokalen Behandlung von Hauterkrankungen in der Haut zu erwarten ist, wurde die Vermehrung menschlicher Fibroblasten gehemmt. Die zur Hemmung erforderliche Konzentration war für Hydrocortison am höchsten und für Clobetasol-17-propionat am niedrigsten. Die Hemmung durch die anderen Steroide (Hydrocortison-17-butyrat, Triamcinolon-acetonid, Betamethason-17-valerat und Hydrocortison-21-acetat) erfolgte im Zwischenbereich. Die Hemmung wurde durch Fluorinierung an sich nicht gesteigert und war unabhängig von der Herkunft dieser Fibroblasten (Baby-Vorhaut oder Armhaut Erwachsenen) und von der Zahl der Passagen (bzw. 17–23 oder 15–16). Mögliche Beziehungen wurden diskutiert zwischen der Hemmung der Zellvermehrung durch diese Steroide einerseits und ihren therapeutischen Effekten bei Psoriasis anderseits, sowie ihre atrophischen Seiteneffekte.

L929 Mäuse-Fibroblasten wurden schon bei 103–104fach niedrigeren Steroidkonzentrationen merklich beeinflußt und der wirksame Bereich war 104–105fach breiter als für primäre menschliche Hautfibroblasten. Daraus folgt, daß diese Mäuse-Fibroblasten ein ungeeignetes Modellsystem für Untersuchungen der in vivo-Effekte von Glucocorticosteroide beim Menschen bilden.

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Ponec, M., de Haas, C., Bachra, B.N. et al. Effects of glucocorticosteroids on primary human skin fibroblasts. Arch. Derm. Res. 259, 117–123 (1977). https://doi.org/10.1007/BF00557951

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