Pimecrolimus does not affect Langerhans cells in murine epidermis.
BACKGROUND
Langerhans cells (LCs) function as specialized antigen-presenting cells in the epidermis, and therefore play a critical role in cutaneous immunological reactions. Topical treatment with corticosteroids is associated with a decrease in epidermal LC number and antigen-presenting capacity in laboratory animals and humans.


OBJECTIVE
To examine whether pimecrolimus, a nonsteroidal inflammatory cytokine inhibitor recently introduced for the topical treatment of atopic dermatitis, differs from corticosteroids in effects on LCs.


METHODS
Groups of BALB/c mice were treated twice daily on one to five consecutive days on the inner surface of the right ear with 10 micro L of ethanolic solutions of the test compounds at their clinically used concentrations (1% pimecrolimus, 0.1% betamethasone-17-valerate, 1% hydrocortisone and 0.05% clobetasol propionate) or with the vehicle (controls) alone. At selected time points after the treatment epidermal sheets were prepared and examined histomorphometrically for LCs immunolabelled with antibodies to major histocompatibility complex (MHC) class II and DEC 205, and adenosine diphosphatase staining.


RESULTS
No changes in number or morphology of LCs were observed in epidermal sheets of mice treated for 5 days with pimecrolimus. In contrast, an almost complete depletion of LCs was observed in skin samples treated with hydrocortisone, betamethasone or clobetasol. Even a single-day treatment schedule with hydrocortisone, betamethasone or clobetasol caused a significant reduction in MHC class II+ LCs, by 31%, 62% and 87%, respectively.


CONCLUSIONS
It is therefore unlikely that topically applied pimecrolimus affects epidermal LCs, in contrast to corticosteroids.
Meingassner
J G
JG
Novartis Forschungsinstitut, Brunnerstrasse 59, A-1235 Vienna, Austria. josef.meingassner@pharma.novartis.com
Kowalsky
E
E
Schwendinger
H
H
Elbe-Bürger
A
A
Stütz
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004817:Epidermis / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; C117268:pimecrolimus; D016559:Tacrolimus