Effect of pimecrolimus vs. corticosteroids on murine bone marrow‐derived dendritic cell differentiation, maturation and function

Effect of pimecrolimus vs. corticosteroids on murine bone marrow‐derived dendritic cell... Abstract: Pimecrolimus (SDZ ASM981) is a non‐steroid member of calcineurin inhibitors recently developed for the treatment of inflammatory skin diseases. In this study, we compared the effect of pimecrolimus and corticosteroids on the differentiation, maturation and function of murine bone marrow‐derived dendritic cells (BM‐DC). We added pimecrolimus at concentrations of 5–500 ng/ml or 0.5 ng/ml mometasone furoate at different timepoints to the BM‐DC culture and checked (i) the number of matured cells, (ii) the expression of activation markers, (iii) the release of cytokines and (iv) the stimulatory capacity of the resulting BM‐DC in vivo. Even at the highest concentration, pimecrolimus treatment resulted in only modest effects. In the pimecrolimus‐treated culture, we observed a decrease in the numbers of matured cells but no significant effects on the expression of activation markers. The release of some inflammatory cytokines was reduced, but the stimulatory capacity in vivo was not affected. In contrast, mometasone furoate has pronounced effects on BM‐DC at a concentration ten to 1000 times lower than those used with pimecrolimus. Furthermore, topical treatment of mice with clobetasole cream 0.05% resulted in almost complete depletion of splenic DC and a severe hyposplenia, while high‐dose oral pimecrolimus treatment did not show any effects on the spleen or on splenic DC. These results support that pimecrolimus, unlike corticosteroids, has little effects on dendritic cells. To the best of our knowledge, this is the first study of this type with use of BM‐DC. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Dermatology Wiley

Effect of pimecrolimus vs. corticosteroids on murine bone marrow‐derived dendritic cell differentiation, maturation and function

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Publisher
Wiley
Copyright
Copyright © 2006 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0906-6705
eISSN
1600-0625
DOI
10.1111/j.0906-6705.2005.00395.x
pmid
16364030
Publisher site
See Article on Publisher Site

Abstract

Abstract: Pimecrolimus (SDZ ASM981) is a non‐steroid member of calcineurin inhibitors recently developed for the treatment of inflammatory skin diseases. In this study, we compared the effect of pimecrolimus and corticosteroids on the differentiation, maturation and function of murine bone marrow‐derived dendritic cells (BM‐DC). We added pimecrolimus at concentrations of 5–500 ng/ml or 0.5 ng/ml mometasone furoate at different timepoints to the BM‐DC culture and checked (i) the number of matured cells, (ii) the expression of activation markers, (iii) the release of cytokines and (iv) the stimulatory capacity of the resulting BM‐DC in vivo. Even at the highest concentration, pimecrolimus treatment resulted in only modest effects. In the pimecrolimus‐treated culture, we observed a decrease in the numbers of matured cells but no significant effects on the expression of activation markers. The release of some inflammatory cytokines was reduced, but the stimulatory capacity in vivo was not affected. In contrast, mometasone furoate has pronounced effects on BM‐DC at a concentration ten to 1000 times lower than those used with pimecrolimus. Furthermore, topical treatment of mice with clobetasole cream 0.05% resulted in almost complete depletion of splenic DC and a severe hyposplenia, while high‐dose oral pimecrolimus treatment did not show any effects on the spleen or on splenic DC. These results support that pimecrolimus, unlike corticosteroids, has little effects on dendritic cells. To the best of our knowledge, this is the first study of this type with use of BM‐DC.

Journal

Experimental DermatologyWiley

Published: Jan 1, 2006

References

  • A novel anti‐inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology
    Grassberger, Grassberger; Baumruker, Baumruker; Enz, Enz
  • Contrasting effects of glucocorticoids on the capacity of T cells to produce the growth factors interleukin 2 and interleukin 4
    Daynes, Daynes; Araneo, Araneo
  • Glucocorticoids down‐regulate dendritic cell function in vitro and in vivo
    Moser, Moser; De Smedt, De Smedt; Sornasse, Sornasse
  • Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus
    Billich, Billich; Aschauer, Aschauer; Aszodi, Aszodi; Stuetz, Stuetz
  • Pimecrolimus does not affect the differentiation, maturation and function of human monocyte‐derived dendritic cells, in contrast to corticosteroids
    Kalthoff, Kalthoff; Chung, Chung; Musser, Musser; Stuetz, Stuetz

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