1. ^*Division of Allergy and Immunology, Department of Pediatrics, The National Jewish Medical and Research Center, Denver, Colorado, USA;
2. ^†Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, USA;
3. ^‡Department of Dermatology, University of Bonn, Bonn, Germany;
4. ^§Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, Roma, Italy;
5. ^¶Division of Dermatology, Department of Medicine and Pediatrics, University of California, San Diego, California, USA;
6. VA San Diego Health Care System, San Diego, California, USA

Correspondence: Donald Y. M. Leung, MD, PhD, National Jewish Medical and Research Center, Department of Pediatrics, Room K926, 1400 Jackson Street, Denver, Colorado 80206, USA. Email: leungd@njc.org

Received 18 November 2004; Revised 25 February 2005; Accepted 1 March 2005.

Abstract

Recurrent skin infections in extrinsic atopic dermatitis (EAD) may be because of the suppression of anti-microbial peptide (AMP) expression by interleukin (IL)-4 and IL-13. Twenty to thirty percent of AD, however, are classified as intrinsic atopic dermatitis (IAD). They exhibit normal serum IgE levels, no allergen-specific sensitization, and lower levels of IL-4 and IL-13 than EAD. Both forms of AD have increased propensity to skin infection, suggesting a novel mechanism for infection in IAD. In this study, we observed significantly decreased human -defensin (HBD)-2 gene expression in the skin of both IAD (p=0.010) and EAD (p=0.004), as compared with psoriasis patients. Conversely, IAD (p=0.019) and EAD (p=0.002) skin lesions exhibited elevated IL-10 gene expression when compared with psoriasis. Using primary keratinocytes, we found that the deficiency in AMP expression is an acquired rather than a constitutive defect. Interestingly, neutralizing antibodies to IL-10 augmented the production of tumor necrosis factor- and interferon- by peripheral blood mononuclear cell from AD patients. Additionally, treatment of AD skin explants with anti-IL-10 augmented the expression of both HBD-2 and LL-37. Thus, increased levels of IL-10 may contribute to the AMP deficiency in both IAD and EAD by reducing cytokines that induce AMP.