title: 1alpha,25-dihydroxycholecalciferol and cyclosporine suppress induction and promote resolution of psoriasis in human skin grafts transplanted on to SCID mice.
abstract: Accumulating evidence has emphasized the importance of immunocompetent cells in determining the psoriatic phenotype. We have investigated the effect of 1alpha,25-dihydroxycholecalciferol, the naturally occurring active form of vitamin D3, cyclosporine A, and interleukin-10 on the phenotype of human psoriatic skin xenotransplants. First, psoriatic skin transplants were injected with either 1alpha,25-dihydroxy- cholecalciferol, cyclosporine A, or interleukin-10. Second, we determined the ability of autologous lymphocytes, activated in vitro using staphylococcal enterotoxin B and interleukin-2 and then exposed to either 1alpha, 25-dihydroxycholecalciferol or cyclosporine A, to induce psoriatic lesions if they were injected into the dermis of uninvolved skin grafts. We found that injections into transplanted psoriatic plaques of either 1alpha,25-dihydroxycholecalciferol or cyclosporine A, but not interleukin-10, resulted in a consistent reduction in the clinical and histologic score of psoriasis with remission towards uninvolved psoriatic skin. Injection of activated immunocytes into symptomless psoriatic skin grafts, changed the grafts towards plaque-type psoriasis with silvery scale, parakeratosis, elongated rete pegs, acanthosis, and dermal angiogenic reaction. In contrast, if activated immunocytes were exposed to 1alpha, 25-dihydroxycholecalciferol or cyclosporine A prior to injection, only minimal changes occurred. It was determined that neither staphylococcal enterotoxin B and interleukin-2 activation by itself, nor the drugs investigated, changed the CD4/CD8 ratio of activated (CD25 + ) cells. Our results are consistent with the hypothesis that psoriasis may be induced by activated T lymphocytes, and indicate that novel immunomodulatory drugs can serve to inhibit the pathogenetic ability of immunocytes in psoriasis.
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor, USA. TNDam@dadlnet.dk
authors.forename: T N
authors.initials: TN
authors.lastname: Dam
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.forename: B J
authors.initials: BJ
authors.lastname: Nickoloff
authors.forename: J J
authors.initials: JJ
authors.lastname: Voorhees
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D002117:Calcitriol / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000627:therapeutic use; D051379:Mice; D016513:Mice, SCID; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016038:Skin Transplantation; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D014183:Transplantation, Heterologous
chemical_list: D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D016572:Cyclosporine; D002117:Calcitriol