Elevated levels of IL-10 in intrinsic (IAD) and extrinsic atopic dermatitis (EAD) is associated with deficiency in anti-microbial peptide (AMP) production

Abstract

Rationale Approximately 10-45% of AD patients are classified as IAD and exhibit normal serum IgE levels, no allergen specific sensitization, and levels of IL-13 lower than EAD patients. However, both IAD and EAD patients exhibit the same clinical disease and suffer from skin infections. These studies were carried out to identify characteristics in IAD and EAD that explain similar propensity to infection. Methods AMP gene expression was evaluated in skin biopsies, peripheral blood mononuclear cells (PBMC), and human keratinocytes using real-time RT-PCR. The immunomodulatory effect of IL-10 was assessed by stimulating human PBMC with anti-CD3 ± IL-10 for 24 hours. Supernatants were added to human keratinocyte cultures to investigate the effect of the PBMC secreted cytokines on the stimulation of AMP. Results HBD-2 gene expression was significantly decreased in explants from both IAD (p=0.024) and EAD (p=0.013), as compared to psoriasis patients. Interestingly, LL-37 expression was significantly decreased in EAD (p=0.027), but not IAD skin, when compared to psoriasis. To investigate the basis for these differences in AMP expression, we examined IL-10. IL-10 expression was significantly elevated in IAD (p=0.044) and EAD (p=0.0006) skin lesions when compared to psoriasis. Supernatants from anti-CD3 stimulated PBMC induced significant increases in the keratinocyte expression of HBD-2 (p=0.008) and LL-37 (p=0.046). Stimulating with anti-CD3 in the presence of IL-10 resulted in a significant decrease in HBD-2 (p=0.04), but not LL-37. Conclusions Increased levels of IL-10 may contribute to the deficiency of HBD-2 in IAD. The combination of IL-10 and IL-13 may suppress HBD-2 and LL-37 in EAD.