Researchers at National Jewish Medical and Research Center report in the October 10 issue of the New England Journal of Medicine that patients with atopic dermatitis, also known as eczema, are susceptible to bacterial infections of their skin because they fail to produce effective amounts of two antimicrobial peptides. The findings demonstrate for the first time the clinical significance of these peptides in humans, and suggest that a medication containing or inducing the peptides may one day be used to fight the infections that plague millions of atopic dermatitis patients. The accompanying editorial in the journal called it a "seminal study."
"This study helps explain why 90 percent of atopic dermatitis patients are colonized by staphylococcus aureus and 30 percent develop active infections," said the study's senior author, Donald Leung, M.D., Ph.D., Head of Pediatric Allergy-Immunology at National Jewish Medical and Research Center, in Denver. "It is important to understand why people with this common skin disease are so susceptible to skin infections, especially in light of recent widespread concerns that they can develop severe infections after receiving a smallpox vaccination. Interestingly, these antimicrobial peptides are also needed to combat viral infections and therefore could account for the susceptibility of atopic dermatitis patients to eczema vaccinatum and herpes simplex infections."
Atopic dermatitis is a common, chronic skin disease characterized by dry, itchy and easily irritated skin. It occurs most commonly in infants and young children, but can persist into adulthood. Severe cases can lead to sleep deprivation, chronic bacterial infections, and depression. Approximately one in nine people in the United States suffer from this disease at some point. Along with other allergic diseases, its prevalence has grown significantly in recent years.
Immunologists recently identified peptides in the skin that help fight incipient infections. They rarely appear in normal skin, but are produced in reaction to skin inflammation. Since atopic dermatitis patients are so frequently plagued by bacterial infections, Dr. Leung and his colleagues decided to investigate the potential role of the antimicrobial peptides in those patients.
They evaluated the levels of two antimicrobial peptides, known as LL-37 and HBD-2, in eight patients with moderate to severe atopic dermatitis, 11 psoriasis patients, and six healthy individuals. Psoriasis is an inflammatory skin disease, whose patients rarely suffer skin infections. Microscopic examination of skin samples showed significant amounts of the peptides in the skin of psoriasis patients, but none to minor amounts in skin from atopic dermatitis patients, and none in the skin of healthy controls. Additional analysis indicated that most psoriasis patients had at least 10 times as much of the peptides in their skin as did atopic dermatitis patients. Many atopic dermatitis patients had no detectable amounts of the antimicrobial peptides in their skin.
When the researchers treated staphylococcus aureus colonies with the antimicrobial peptides, levels found in skin of psoriasis patients killed the bacteria. The researchers also found that two hormone-like proteins associated with the immune response and commonly secreted by atopic dermatitis patients' cells, IL-4 and IL-13, suppressed the production of HBD-2 in cell cultures.
"These findings indicate that atopic dermatitis patients have an impaired immune response that prevents them from producing adequate amounts of antimicrobial peptides in their skin," said Dr. Leung.
The research suggests that the missing peptides might one day be used as a treatment to prevent skin infections in atopic dermatitis patients. "Our body normally makes these peptides to fight infections, so there might be fewer side effects than with conventional antibiotics," said co-author Richard Gallo, M.D., Ph.D., Chief of Dermatology at the Veterans Affairs San Diego Healthcare System and Associate Professor of Medicine at the University of California, San Diego. In 1994, Dr. Gallo was the first to discover the antimicrobial peptides in mammalian skin. The peptides might have another advantage over conventional antibiotics, said Dr. Gallo. While conventional antibiotics attack only bacteria, the antimicrobial peptides fight bacteria, viruses and fungi.
Researchers will also be working in the next several years to alter the immune response of atopic dermatitis patients to promote the production of the antimicrobial peptides, said Dr. Leung.
The findings could shed light on atopic dermatitis patients' susceptibility to eczema vaccinatum, a widespread skin infection that can afflict those who receive the smallpox vaccination. They may have relevance for other diseases, as well. For instance, it is known that tuberculosis and leprosy patients, whose cells secrete the same immune system regulators as atopic dermatitis patients, are more likely to have disease that spreads widely in their bodies.
Funding for the research was provided by the Veterans Affairs; The National Institutes of Health; the University of Colorado Cancer Center; the Academy of Allergy, Asthma and Immunology; and the Stern Foundation.
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