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Eczema Tied to Failure of Natural Antibiotic

Discovery could lead to better therapy, understanding of other diseases

WEDNESDAY, Oct. 9, 2002 (HealthDayNews) -- The recurrent infections suffered by people with the most common form of eczema are due to the failure of a newly discovered defense system that produces microbe-fighting molecules in the skin and other organs.

"We've known about these natural peptide antibiotics in lower animals, but there hadn't been any examples in humans that associated them with a disease," says Dr. Richard Gallo, chief of dermatology with the Veterans Affairs San Diego Healthcare System. Gallo is a member of the research team reporting the finding on this kind of eczema, known as atopic dermatitis, in tomorrow's issue of The New England Journal of Medicine.

"This gives us greater insight into the disease and might make clinicians more cognizant of the risk of infection for these patients," Gallo says. "We hope that within five years or so it will lead to a more rational design of antibiotic replacements for these patients."

However, the report has significance far beyond any skin condition, says Dr. Michael Zasloff, dean of research at Georgetown University Medical Center and author of an accompanying editorial. To him, it is an opening chapter of a medical story that ranks in significance with Pasteur's discovery of vaccination.

What Pasteur and others since then have regarded as the first line of defense, the system housed in the bone marrow that produces protective cells that fight invaders, is actually a backup for a "powerful, silent, innate" system that quietly manufactures molecules to fight microbes, viruses and fungi, Zasloff says.

"This becomes evident when you look at most of the animals on the planet," he says. "If you forget about vertebrates, you realize that most of the other creatures rely exclusively on the innate system for survival. We and other vertebrates have inherited a second system, above and beyond the innate system."

Acute dermatitis is an inherited disease that affects upwards of 3 percent of Americans, and is most common in childhood. The condition causes infections to occur again and again because skin cells do not produce natural antimicrobial compounds called cathelicidins and beta-defensins, the journal report says. Gallo first described those molecules in 1994.

As part of the study, researchers at the National Jewish Medical and Research Center in Denver showed the antimicrobial molecules work together to kill Staphylococcus aureus, a common cause of skin infections. When they compared skin samples from eight patients with atopic dermatitis, 11 patients with psoriasis and six healthy persons, they found elevated levels of the defense molecules in the psoriasis patients, a response to an infectious attack, but not in the atopic dermatitis patients, an indication that they were not responding properly to such an attack.

"The most frequent complication of atopic dermatitis is that the skin gets infected frequently," Gallo says. "Our finding that these natural peptide antibiotics are deficient in patients may explain why they get infections."

Similar defects in this innate system could explain many other human diseases, says Zasloff. A study to be published next week will show a link with periodontal disease, in which white cells fail to make the microbe-fighting molecules, he says.

"I am interested in disorders of the bowel," he says. "There is a fair amount of work going on in many laboratories that has not yet been published, which suggests that certain disorders, such as inflammatory bowel disease, are in fact problems with the innate immune system."

"This innate system keeps microbes at bay with very little energy and little tissue damage. When it fails us, the deeper second line of defense gets pulled in, and when that is mobilized all hell breaks loose."

Pharmaceutical companies are starting to get interested in these defensive molecules, Gallo says. "A number of companies have been looking at them," he says. "There are possible clinical applications, like diabetic ulcers and infections of the mouth."

And so, Zasloff says, "what seems to be a rather arcane finding touches upon the importance of the innate defenses system."

What To Do

Information about atopic dermatitis is given by the American Academy of Dermatology or the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

SOURCES: Richard Gallo, M.D., Ph.D., chief, dermatology, Veterans Affairs San Diego Healthcare System; Michael Zasloff, M.D., Ph.D., dean, research, Georgetown University Medical Center, Washington, D.C.; Oct. 10, 2002, The New England Journal of Medicine
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