Pathogenic function of IL-1β in psoriasiform skin lesions of flaky skin (fsn/fsn) mice

Abstract

Summary IL-1 acts on many cells as an inflammatory mediator. Its two forms, IL-1α and IL-1β, are regulated differentially within hyperproliferative inflammatory skin conditions, such as psoriasis. While IL-1α is down-regulated within psoriatic lesions, the levels of IL-1β are increased. However, some investigators have described an inactive form of IL-1β in psoriasis, while others have detected increased IL-1β activity within these lesions. Thus, its in vivo role remains unclear. We have assessed expression and function of IL-1β within psoriasiform skin lesions of the spontaneous mouse mutation flaky skin (fsn/fsn). It was found that IL-1β 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-1β 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-1β for the generation of hyperproliferative inflammatory skin lesions in the fsn/fsn model.