1. ¹Department of Dermatology and Allergy, Allergy-Center-Charité Campus Mitte Universitätsmedizin Berlin, Berlin, Germany
2. ²Department of Molecular Parasitology, Humboldt–University Berlin, Berlin, Germany

Correspondence: Dr Margitta Worm, Department of Dermatology and Allergy, Charité–Universitätsmedizin Berlin (CCM), Charitéplatz 1, Berlin 10117, Germany. E-mail: margitta.worm@charite.de

Received 17 September 2007; Revised 1 February 2008; Accepted 9 February 2008; Published online 10 April 2008.

Abstract

We have shown previously that specific ligands of the peroxisome proliferator-activated receptor- (PPAR) inhibit the systemic allergic immune response. The objective of this study was to investigate the impact of PPAR-ligand treatment on the local allergic immune response. We established a murine model exhibiting clinical and histological features of AD-like skin lesions with high reproducibility. In this model, the PPAR ligand was applied in an either preventive or therapeutic manner via systemic and local routes. The affected skin areas were assessed by standardized skin score, histological analyses, and immunohistochemical examinations. Our data show that systemic application of PPAR ligand by a preventive protocol led to significantly reduced onset of eczematous skin lesions. This was confirmed by histology, showing decreased skin thickness accompanied by significantly reduced infiltrations of CD4+ and CD8+ lymphocytes but also mast cells. Additionally, early allergen-specific IgE and IgG1 responses were reduced (day 21/35), whereas IgG2a levels remained unchanged. In conclusion, our results demonstrate that PPAR-ligand treatment inhibits not only systemic allergic immune response, but also local allergen-mediated dermatitis. Our findings point to therapeutic strategies, including a PPAR-ligand-based treatment.