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 al pha and IL-1 beta, are regulated differentially within hyperproliferative i nflammatory skin conditions, such as psoriasis. While IL-1 alpha is down-re gulated within psoriatic lesions, the levels of IL-1 beta are increased. Ho wever, some investigators have described an inactive form of IL-1 beta in p soriasis, while others have detected increased IL-1 beta activity within th ese lesions. Thus, its in vivo role remains unclear. We have assessed expre ssion and function of IL-1 beta within psoriasiform skin lesions of the spo ntaneous mouse mutation flaky skin (fsn/fsn). It was found that IL-1 beta w as increased by 357% within psoriasiform lesions of fsn/fsn mice compared w ith their wild-type or heterozygous (+/?) littermates (P < 0.00001). When t he IL-1 beta function was inhibited by i.p. injection with a neutralizing M oAb, no effects were seen in +/? mice. In contrast, psoriasiform features i n fsn/fsn mice were alleviated dramatically, as demonstrated by a 40% decre ase of the epidermal thickness and a diminished number of intra-epidermal m icroabscesses. In addition, infiltrating epidermal CD4(+) and CD8(+) T cell s were decreased by 68% and 81%, respectively (P < 0.05), and epidermal Lan gerhans 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 f sn/fsn model.