Effect of pimecrolimus vs. corticosteroids on murine bone marrow-derived dendritic cell differentiation, maturation and function.
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.
Krummen
Mathias B W
MB
Department of Dermatology, University of Münster, Germany. el.pc@gmx.de
Varga
Georg
G
Steinert
Meike
M
Stuetz
Anton
A
Luger
Thomas A
TA
Grabbe
Stephan
S
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000954:Antigens, Surface / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002990:Clobetasol / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D000068656:Mometasone Furoate; D010641:Phenotype; D011244:Pregnadienediols / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000954:Antigens, Surface; D015850:Interleukin-6; D011244:Pregnadienediols; D014409:Tumor Necrosis Factor-alpha; D000068656:Mometasone Furoate; D018664:Interleukin-12; C117268:pimecrolimus; D007371:Interferon-gamma; D002990:Clobetasol; D016559:Tacrolimus