Penn Medical Study Offers Hope On Skin Disease And More

Posted: November 15, 1989

Scientists at the University of Pennsylvania report that they have discovered how skin inflammation occurs at the molecular level, a finding that could lead to new drugs for the 30 million Americans suffering from skin diseases.

The study might also lead to new therapies for treating sufferers of asthma, arthritis and other diseases in which inflammation plays a role, the researchers said.

In addition, the findings suggest that there is scientific evidence to support the widespread belief that anxiety and stress make itching, eczema, psoriasis and other skin diseases worse.

"These findings may open the door to the development of new therapies," said George Murphy, a dermatology professor at Penn's medical center and one of the authors of the study, which is being published today in the journal Proceedings of the National Academy of Sciences.

"In the past, drug therapies, such as steroids, have been used to treat skin inflammation after it has occurred," Murphy said. "With our new understanding of the inflammation process, it may be possible to develop drugs that prevent skin inflammation before it occurs."

The study's authors said, however, that people shouldn't expect new drugs soon. Pharmaceutical products can take many years to be developed, tested, approved and marketed.

Gerald Lazarus, chairman of Penn's dermatology department, said he believed the findings are "very important" because inflammation aggravates many diseases. "This study has implications for treating asthma, rheumatoid arthritis and possibly even skin cancer," he said.

Inflammation, which is the redness and swelling of tissues, occurs when the body's tissues are injured or infected.

The scientists' study focuses on the role that "mast cells" play in the inflammation process. These cells, which are found in most body tissues but are particularly numerous in the innermost layer of the skin, play a key role in the body's allergic response. However, until now scientists were not aware of just how important that role may be.

Murphy and other members of the Penn team now believe that mast cells help trigger the inflammation process. Their research shows that tiny nerve fibers in these cells cause the release of a chemical known as substance P.

According to the new study, substance P causes the mast cells to release dense chemical granules. One of these chemicals is histamine, which causes blood vessels to leak and leads to the buildup of fluids under the skin. Another chemical, known as tumor necrosis factor, makes certain cells ''sticky" for white blood cells, which then accumulate in those tissues.

The Penn team's findings counter the previously held view that mast cells release chemicals after inflammation occurs, and assert instead that mast cells initiate the process. "Mast cells may be the critical initiator of all inflammation," Murphy said.

The scientists used small pieces of human skin, obtained from the discarded foreskins of circumcised babies and from Murphy's own upper arms, to discover the process. They used morphine and other chemicals to cause mast cells in the skin to release chemical granules.

They then used powerful electron microscopes and other scientific tools to study the inflammation process at the molecular level.

Murphy said the scientists' findings have implications for the development of new drugs for treating psoriasis, eczema, acne and other skin ailments. He said it may be possible to develop drugs that "nip in the bud" inflammation by inhibiting the release of chemicals from the mast cells. Current treatments merely suppress existing inflammation.

Penn researchers estimated that about four million Americans suffer from psoriasis, 12 million have eczema or dermatitis and 18 million suffer from acne.

Lazarus said the discoveries about the inflammation process could also lead to the development of drugs for the treatment of asthma, rheumatoid arthritis, digestive ailments and possibly skin cancer. Mast cells play a role in all of these diseases.

And because tiny nerve cells seem to trigger the whole process, Murphy said their findings support the growing body of evidence that suggests a link between the nervous system and immunity.

"There is now some evidence to show that, at least on the skin, the immune response is controlled to some extent by state of mind and emotional status," he said. "For dermatologists, this is remarkably significant because of the observation that has been held for hundreds of years that anxiety and stress can provoke itching or cause a worsening of such (diseases) as psoriasis and eczema."

Other members of the Penn research team are Lynn Klein, Wendy Matis, Robert Lavker and Diana Whitaker. Their research was supported by a $3.5 million grant awarded earlier this year from the National Institutes of Arthritis, Neuromuscular and Skin Diseases.

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