Eczema patients lack natural antibiotic in skin.
Eczema Patients Lack Natural Antibiotic In Skin
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.