title: Pimecrolimus inhibits the elicitation phase but does not suppress the sensitization phase in murine contact hypersensitivity, in contrast to tacrolimus and cyclosporine A.
abstract: Pimecrolimus (SDZ ASM 981, Elidel) is a nonsteroid inflammatory cytokine inhibitor specifically developed for the treatment of inflammatory skin diseases. Its effect on the elicitation and sensitization phases of oxazolone-induced contact hypersensitivity was compared with tacrolimus and cyclosporine A (CyA) in BALB/c mice using the ear swelling assay. The compounds were administered orally. Elicitation was dose-dependently inhibited by all three compounds. The minimal effective doses were 30 mg per kg (pimecrolimus, tacrolimus) and 90 mg per kg (CyA), respectively. There was no impairment of sensitization by pimecrolimus up to the highest dose tested (120 mg per kg), in contrast to CyA (60% inhibition at 60 mg per kg) and tacrolimus (71% inhibition at 30 mg per kg). Weight and cellularity of the draining lymph nodes in mice treated with tacrolimus or CyA during sensitization were reduced. In addition, proliferation of T cells after secondary stimulation was inhibited in cell cultures from lymph nodes of mice treated with tacrolimus or CyA. Thus, in contrast to tacrolimus and CyA, pimecrolimus exerts a more selective immunomodulatory effect. It does not impair the primary immune response (sensitization phase) but effectively inhibits the secondary phase, the elicitation phase that is the clinical manifestation of contact hypersensitivity.
authors.affiliation: Novartis Research Institute, Vienna, Austria. josef.meingassner@pharma.novartis.com
authors.forename: Josef G
authors.initials: JG
authors.lastname: Meingassner
authors.forename: Hermann
authors.initials: H
authors.lastname: Fahrngruber
authors.forename: Assadollah
authors.initials: A
authors.lastname: Bavandi
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003879:Dermatologic Agents / Q000494:pharmacology*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000166:cytology; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D003879:Dermatologic Agents; D007166:Immunosuppressive Agents; C117268:pimecrolimus; D016572:Cyclosporine; D016559:Tacrolimus