Embargoed by the New England Journal of Medicine For Release at 5 pm EDT October 9, 2002

Lack of Natural 'Antibiotics' in the Skin
May Explain Infections in Dermatitis Patients

In a study published in the Oct. 10, 2002 New England Journal of Medicine, scientists report that people with atopic dermatitis--the most common form of eczema--fail to produce germ-killing peptides that fight infections in other inflammatory skin diseases, such as psoriasis. The finding may lead to a new type of antimicrobial cream, based on the body's own chemicals, that stems infections and heals skin for millions of American children and adults with this distressing chronic illness.

Richard Gallo, M.D., Ph.D.

"This may explain why people with atopic dermatitis get infections," said co-investigator Richard Gallo, M.D. Ph.D., UCSD associate professor of medicine and chief of dermatology with the Veterans Affairs San Diego Healthcare System. Gallo, who in 1994 was the first to discover antimicrobial peptides in mammalian skin, worked on this study with investigators at the Denver-based National Jewish Medical and Research Center and other sites.

When the skin is penetrated by pathogens, an army of white blood cells, aided by various biochemicals, attacks the invader to prevent infection. However, this immune response does not appear to happen readily in atopic dermatitis patients, who often suffer recurring skin infections.

Atopic dermatitis is an inherited disease usually accompanied by asthma and allergies. It is marked by red, itchy, swollen skin. The disease accounts for about 15 percent of dermatologist visits in the United States.

Scientists have only recently identified a class of compounds known as cathelicidins and beta defensins that play a key role in the immune response of the skin and other organs by killing bacteria, viruses and fungi. These antimicrobial compounds are peptides, groups of amino acids that link to form proteins. Last year, Gallo published a study in the journal Nature showing that these peptides are important in protecting mice against certain bacteria.

In this new study, led by Donald Y. M. Leung, M.D., Ph.D., of NJMRC and the University of Colorado Health Sciences Center, researchers have shown for the first time that a shortage of these peptides may account for human skin infections, such as those in dermatitis.

"Understanding this was a big question in understanding the disease of atopic dermatitis," said Leung.

Researchers analyzed skin samples from 6 healthy adults; 8 patients with atopic dermatitis; and 11 patients with psoriasis, another common inflammatory skin disease. The normal skin contained almost no antimicrobial peptides, as these compounds are made only as needed. The psoriatic skin showed high levels, as is typical for many inflammatory skin conditions. But the skin with dermatitis contained much lower levels, almost like the normal skin.

The study also showed that cathelicidins and beta-defensins work together to kill the bacteria staphylococcus aureus, a common culprit in dermatitis infections. According to Gallo, a drug containing these natural antimicrobial peptides would protect dermatitis sufferers not only from bacteria, but also from viruses and funguses--common problems for dermatitis patients. Current antibiotic creams work only against bacteria.

Gallo noted other potential advantages of a peptide-based cream over existing treatments for inflammatory skin disease. "It might be more potent and would act on the skin to help healing, so the damage in atopic dermatitis would repair more quickly," he said. "And our body normally makes these peptides to fight infection, so there might be fewer side effects than with conventional antibiotics."

He added that unlike conventional antibiotics, peptide-based antibiotics "have been around for tens of thousands of years, and still seem important to our body to fight infection."

Gallo and Leung both believe the peptides may be particularly useful as drugs. They caution, however, that their use as a drug would have to be watched carefully for signs of eventual resistance among pathogens.

Other researchers on the study included lead authors Peck Y. Ong, NJMRC; Takaaki Ohtake, VA and UCSD; and Corinne Brandt, VA and UCSD; and co-investigators Ian Strickland, NJMRC; Mark Boguniewicz, NJMRC and UCHSC; and Tomas Ganz, University of California, Los Angeles.

Funding for the research was provided by VA; 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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