Pathogenic function of IL-1 beta in psoriasiform skin lesions of flaky skin (fsn/fsn) mice.
IL-1 acts on many cells as an inflammatory mediator. Its two forms, IL-1 alpha and IL-1 beta, are regulated differentially within hyperproliferative inflammatory skin conditions, such as psoriasis. While IL-1 alpha is down-regulated within psoriatic lesions, the levels of IL-1 beta are increased. However, some investigators have described an inactive form of IL-1 beta in psoriasis, while others have detected increased IL-1 beta activity within these lesions. Thus, its in vivo role remains unclear. We have assessed expression and function of IL-1 beta within psoriasiform skin lesions of the spontaneous mouse mutation flaky skin (fsn/fsn ). It was found that IL-1 beta was increased by 357% within psoriasiform lesions of fsn/fsn mice compared with their wild-type or heterozygous (+/?) littermates (P < 0.00001). When the IL-1 beta function was inhibited by i.p. injection with a neutralizing MoAb, no effects were seen in +/? mice. In contrast, psoriasiform features in fsn/fsn mice were alleviated dramatically, as demonstrated by a 40% decrease of the epidermal thickness and a diminished number of intra-epidermal microabscesses. In addition, infiltrating epidermal CD4(+) and CD8(+) T cells were decreased by 68% and 81%, respectively (P < 0.05), and epidermal Langerhans cells also were reduced by 36% (P < 0.005). In contrast, mast cells were not affected, suggesting differential responses of various cutaneous cell types. Our results demonstrate an important in vivo role of IL-1 beta for the generation of hyperproliferative inflammatory skin lesions in the fsn/fsn model.
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Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany. michael.schoen@medizin.uni-magdeburg.de
Behmenburg
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Denzer
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Schön
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D000818:Animals; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009500:Neutralization Tests; D011565:Psoriasis / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000473:pathology*
D007375:Interleukin-1