In vivo effects of cytokines on psoriatic skin grafted on nude mice: involvement of the tumour necrosis factor (TNF) receptor.
Following engraftment of human involved psoriatic skin to nude mice there is a partial normalization of pathology associated with a loss of inflammatory leucocytes. However, the epidermis remains hyperproliferative, which may reflect a primary defect. The roles of TNF-alpha, IL-1 and IL-6 in epidermal hyperproliferation of grafted psoriatic lesions were investigated. Before and after treatment, grafts were analysed to determine epidermal thickness and labelling index (LI). HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and TNF receptor (TNF-R; p75 and p55) expression were determined by immunoperoxidase staining. Psoriatic epidermis was found consistently to be negative for p55 TNF-R and p75 TNF-R before grafting. Following engraftment, TNF-R-positive cells (i.e. p55 by keratinocytes; p75 by epidermal dendritic cells) were identified throughout the epidermis. Higher numbers of p75 TNF-R epidermal dendritic cells were found in grafts following a course of TNF-alpha, IL-6 or IL-1 treatment. The p55 form of the TNF-R expressed by keratinocytes was significantly elevated after treatment with TNF-alpha or IL-6. HLA-DR and ICAM-1 were also expressed in these grafts. TNF-alpha, anti-IL-1, and anti-IL-6 treatment induced a marked decrease in the epidermal thickness and LI of psoriatic graft tissue, correcting the hyperproliferation associated with psoriatic epidermis. Supraphysiological levels of TNF-alpha may saturate and consequently down-regulate their own receptors, leading to a paradoxical inhibitory effect.
Gilhar
A
A
Skin Research Laboratory, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
David
M
M
Kalish
R S
RS
Weisinger
G
G
D000818:Animals; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D004817:Epidermis / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D006801:Humans; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011565:Psoriasis / Q000209:etiology* / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D016038:Skin Transplantation / Q000276:immunology* / Q000473:pathology*; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014183:Transplantation, Heterologous
D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor; D010959:Tissue Plasminogen Activator