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. 2001 Mar;123(3):505-10.
doi: 10.1046/j.1365-2249.2001.01421.x.

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

M Schön  1 , C Behmenburg, D Denzer, M P Schön
Affiliations

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

M Schön et al. Clin Exp Immunol. 2001 Mar.

Abstract

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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Figures

Fig. 1
Fig. 1
IL-1β expression is elevated within psoriasiform lesions of fsn/fsn mice compared with +/? littermates. (a) IL-1β was quantitatively assessed by ELISA using equal amounts of total protein from whole-skin extracts of +/? mice (□) and fsn/fsn mice (▪) as outlined in Materials and Methods. The columns represent average amounts of IL-1β from six animals in each group (± s.d.). *P < 0·00001. (b) IL-1β was detected by immunohistochemistry in 5-μm sections of dorsal skin from a +/? mouse (left panel) and a fsn/fsn mouse (right panel). Scale bar = 20 μm. The panels shown are representative of similar results seen with five animals in each group.
Fig. 2
Fig. 2
In vivo neutralization of IL-1β alleviates psoriasiform skin lesions in fsn/fsn mice. +/? mice (left panel) and fsn/fsn mice (middle and right panels) were injected intraperitoneally with an isotype-matched control MoAb (middle panel) or the anti-IL-1β MoAb 30311.11 (left and right panels) as described in Materials and Methods. Dorsal skin was harvested 9 days after initiation of the treatment, and 3 μm paraffin-embedded sections were stained by haematoxylin and eosin. The dashed lines indicate the location of the dermo–epidermal junction. Scale bar = 20 μm. The panels shown are representative of five mice in each treatment group.
Fig. 3
Fig. 3
In vivo neutralization of IL-1β differentially affects cutaneous cell types in fsn/fsn mice. (a) Homozygous mutant fsn/fsn mice (n = 5 in each group) were treated by i.p. injections with an isotype-matched control MoAb (upper row) or the IL-1β-neutralizing MoAb (lower row). Leucocyte antigens were detected by immunohistochemistry as indicated in 5-μm cryostat-cut sections of dorsal skin. The panels shown are representative of five mice in each treatment group. Scale bar = 20 μm. (b) +/? mice (n = 5) and fsn/fsn mice (n = 5) were injected as outlined in (a) paraffin-embedded sections (3 μm) of dorsal skin from anti-IL-1β-treated +/? mice (left), isotype-treated fsn/fsn mice (middle panel) and anti-IL-1β-treated fsn/fsn mice (right) were Giemsa-stained. Cutaneous mast cells are visualized as dark purple cells. Scale bar = 20 μm.
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