ENDOGENOUS ANTIMICROBIAL PEPTIDES AND SKIN INFECTIONS IN ATOPIC DERMATITIS

Abstract

Ong PY, Ohtake T, Brandt C, et al. N Engl J Med. 2002;347:1151–1160The immune system of human skin contains several antimicrobial peptides, particularly cathelicidins (LL-37) and β-defensins. Although these peptides are negligible in normal skin, they accumulate in skin affected by inflammatory diseases such as psoriasis. The purpose of this study was to compare the levels of expression of LL-37 and human β-defensin 2 (HBD-2) in inflamed skin from patients with atopic dermatitis and from those with psoriasis.Patients with atopic dermatitis or psoriasis were compared with normal controls with no skin disease.The expression of LL-37 and HBD-2 protein in skin biopsy specimens was determined by immunohistochemical analysis. The amount of antimicrobial peptides in extracts of skin samples was also analyzed by immunodot blot analysis (for LL-37) and Western blot analysis (for HBD-2). Reverse transcriptase-polymerase chain reaction (RT-PCR) assays were used to confirm the relative expression of HBD-2 and LL-37 messenger RNA (mRNA) in the skin-biopsy specimens. These peptides were also tested for antimicrobial activity against Staphylococcus aureus with the use of a colony-forming assay.Immunohistochemical analysis confirmed the presence of abundant LL-37 and HBD-2 in the superficial epidermis of all patients with psoriasis. In comparison, immunostaining for these peptides was significantly decreased in acute and chronic lesions from patients with atopic dermatitis (P = .006 and P = .03, respectively). RT-PCR showed significantly lower expression of HBD-2 mRNA and LL-37 mRNA in atopic lesions than in psoriatic lesions (P = .009 and P = .02, respectively). The combination of LL-37 and HBD-2 showed synergistic antimicrobial activity by effectively killing S aureus.A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S aureus.It has long been recognized that patients with atopic dermatitis have an enormous predilection for cutaneous infections with S aureus, as well as viral pathogens. Although this could be attributable in part to damage to the skin through excessive scratching, it has also been presumed that specific immunologic mechanisms must also play a role. This study elegantly unravels at least part of the immunologic basis for this common clinical problem.