New Study Uncovers the Dark Side of ATP

Researchers have found that one of the most common and hard-working substances in the body may have a Jekyll and Hyde quality in rosacea patients, assuming a darker role when activated by flare-up triggers.

"Sometimes too much of a good thing turns out to be bad," noted Dr. Richard Granstein, chairman of dermatology at Cornell University, lead investigator in the ongoing research funded by the National Rosacea Society (NRS). "The key to improving therapy is to identify those inflammatory pathways involved with rosacea so they can be better controlled."

The researchers have discovered that when adenosine 5'-triphosphate (ATP) -- a neurotransmitter and carrier of chemical energy throughout the body -- is released into the skin by the nerves, a cascade of microscopic events may occur in rosacea patients that ultimately leads to the bumps and pimples of subtype 2 (papulopustular) rosacea.

"As with many disorders, inflammation represents a normal body process gone awry," Dr, Granstein explained. Inflammation is a protective response to injury or destruction of tissues that serves to destroy, dilute or wall off both the agent of injury and the injured tissue, so that tissue can repair itself.

The most evident outward signs and symptoms of inflammation are pain, heat, redness, swelling and loss of function. However, the biochemical processes that accomplish this reaction are complex, and involve dilation of blood vessels accompanied by increased blood flow, release of fluids and the movement of leukocytes -- blood cells that engulf and digest bacteria and fungi and are an important part of the body's defense system, according to Dr. Granstein.

While ATP has many functions in the body, its role in the development of rosacea may involve its job as a messenger from the nerves. The nervous system regulates blood flow to the skin, using ATP to prompt the dilation of blood vessels following exposure to rosacea triggers such as sunlight, emotional stress or alcohol. This process may result in the flushing and redness of subtype 1 (erythematotelangectatic) rosacea.

According to Dr. Granstein, ATP has also been shown to be involved in the movement and buildup of leukocytes onto endothelial cells -- cells that line the blood vessels. In rosacea, the researchers found that endothelial cells respond to ATP with changes in the expression of inflammatory cytokines and other substances that act to recruit inflammatory cells and may lead to rosacea's bumps and pimples.

"As we continue to learn more about the biochemical processes that lead to rosacea, we should increasingly be able to identify how signs and symptoms occur in order to develop appropriate means to prevent them," Dr. Granstein said. He noted that, while current therapies may block some of these pathways, the process is still unclear and should become increasingly evident through continuing research.

In previous NRS-funded studies, Dr. Granstein's team demonstrated that ultraviolet B (UVB) radiation, which is found in sunlight and causes sunburn, may increase vascular endothelial growth factor (VEGF), a regulator of blood vessel growth that may cause visible blood vessels (telangiectasia) associated with subtype 1 rosacea. In addition, they found that UVB may increase interleukin 8, which plays a role in inflammation.

For more information on results of NRS-funded studies, visit the Research Results page in the research grants section.