1. ¹Division of Rheumatology, University Hospital, Geneva, Switzerland
2. ²Department of Pathology and Immunology, University of Geneva School of Medicine, Geneva, Switzerland
3. ³Department of Dermatology, University Hospital, Geneva, Switzerland

Correspondence: Dr Cem Gabay, Division of Rheumatology, University Hospital, 26 av. Beau-Séjour, Geneva 14 1211, Switzerland. E-mail: Cem.Gabay@hcuge.ch

Received 17 November 2006; Revised 10 January 2007; Accepted 26 January 2007; Published online 3 May 2007.

Abstract

The IL-1 system plays a key role in skin physiology and pathology. In this study, we used mutant mice lacking the type I IL-1 receptor (IL-1RI), lacking IL-1 receptor antagonist (IL-1Ra), or overexpressing the human intracellular (ic) IL-1Ra1 isoform, as well as combinations thereof, to dissect the role of the IL-1 system in phorbol 13-myristate 12-acetate (PMA)-induced skin inflammation. In wild-type (WT) mice, PMA application induced epidermal thickening and dermal inflammation. Skin IL-1 production and circulating levels of the acute-phase protein serum amyloid A (SAA) were elevated. In mice lacking IL-1RI or overexpressing icIL-1Ra1, PMA induced similar epidermal thickening as in WT mice, but dermal inflammation was partially prevented. Skin IL-1 mRNA expression was similar in PMA-treated IL-1RI-/- and WT mice, whereas the increase in serum SAA was suppressed in IL-1RI-/- mice. Interestingly, PMA-induced IL-1 mRNA expression was further enhanced by icIL-1Ra1 overexpression in an IL-1RI-dependent manner. Finally, IL-1Ra-/- mice spontaneously displayed skin lesions characterized by high IL-1, but not IL-1, expression. In conclusion, PMA-induced epidermal thickening and skin IL-1 expression were independent of IL-1 signaling, in contrast to dermal inflammation and systemic inflammatory response.