In vivo effects of cytokines on psoriatic skin grafted on nude mice: Involvement of the tumour necrosis factor (TNF) receptor

A. Gilhar*, M. David, R. S. Kalish, G. Weisinger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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-α, 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-α, IL-6 or IL-1 treatment. The p55-form of the TNF-R expressed by keratinocytes was significantly elevated after treatment with TNF-α or IL-6. HLA-DR and DR and ICAM-1 were also expressed in these grafts. TNF-α, 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-α may saturate and consequently down-regulate their own receptors, leading to a paradoxical inhibitory effect.

Original languageEnglish
Pages (from-to)134-142
Number of pages9
JournalClinical and Experimental Immunology
Volume106
Issue number1
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • IL-1
  • IL-6
  • Psoriasis
  • TNF receptors
  • Tumour necrosis factor

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