It is known that keratinocytes produce and secrete interleukin-1 (IL-1) de novo and that this process can be enhanced by various stimulators. IL-1 has been shown to be a potent proin-flammatory cytokine which mediates inflammation in various cutaneous disorders. It has also been demonstrated that Γ-interferon (IFN-Γ) which is released from infiltrated T cells can be detected in inflamed lesional sites. In order to understand the effects of IFN-Γ on IL-1 production by keratinocytes in such inflammatory lesions, normal human keratinocytes (NHKs) and human squamous cell carcinoma cell line (HSC-1) cells were cultivated with recombinant human IFN-Γ (rIFN-Γ) and IL·1 levels were measured by ELISA. The effects of antipsoriatic agents such as hydrocortisone (HC), cyclosporine A(CsA), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and its analogue MC903 on IL-1 production by keratinocytes were also investigated. IL-1 release by both NHK and HSC-1 cells was accelerated by stimulation with rIFN-Γ dose-dependently, although IL-1Α was released only transiently by rlFN-Γ-stimu-lated NHKs in serum-free keratinocyte growth medium containing HC. Antihuman IFN-Γ antibody inhibited IL-lΑ release by HSC-1 cells stimulated with rIFN-Γ, suggesting that IL-1Α release from keratinocytes is upregulated by IFN-Γ. HC (5 µg/ml), 1,25(OH)2D3 (10-6M) and MC903 (10-6 M), but not CsA (5 µg/ml), inhibited IL-lΑ production by HSC-1 cells stimulated with 100 U/ml of rIFN-Γ. Since IL-l plays an important role in the initiation of cutaneous inflammation, its downregulation may prevent inflammation and thereby at least partly account for the clinical effectiveness of these agents in the treatment of psoriasis.

Keywords:
γ-Interferon, Interleukin-1, Keratinocytes, Antipsoriatic agents
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© 1995 S. Karger AG, Basel
1995
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