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.
Note: This story has been
adapted from a news release issued by National Jewish Medical And Research
Center for journalists and other members of the public. If you wish to quote
from any part of this story, please credit National Jewish Medical And Research
Center as the original source. You may also wish to include the following link
in any citation:
ALL INFORMATION, DATA, AND
MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION
PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS
OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR
LEGAL ADVICE. THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND
COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH
YOUR HEALTH CARE PROVIDER.
"A foolish faith in authority is the worst enemy of truth."
-- Albert Einstein, letter to a friend, 1901
"I know of no safe depository of the ultimate powers of the society but the people themselves, and if we think them not enlightened enough to exercise control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion by education."
-- Thomas Jefferson, letter to William C. Jarvis, September 28, 1820
"What's the point of vaccination if it doesn't protect you from the unvaccinated?"
-- Sandy Gottstein
"Who gets to decide what the greater good is and how many will be sacrificed to it?"