Innate immunity: Role in rosacea?




June 1, 2004
By: Michelle Stephenson
Dermatology Times





San Diego - The innate immune system may play a role
in rosacea, according to Richard L. Gallo, M.D.,
Ph.D., from the Veterans Medical Research Foundation
here and the University of California San Diego.

"Innate immunity is an aspect of the immune system
that doesn't require prior exposure to an antigen,"
Dr. Gallo says. "In other words, we have a genetically
programmed ability to respond to danger in our
environment. All animals have this kind of system
programmed into their genes."

Innate immunity
He notes that many aspects of the way the skin defends
itself against danger is through innate immunity. His
laboratory has studied one of the weapons of innate
immunity - antimicrobial peptides.

Antimicrobial peptides called cathelicidins, have
effects that look like rosacea. They cause blood
vessels to grow, and they affect the attraction of
inflammatory cells such as histiocytes into the skin.
Dr. Gallo has found that patients with rosacea have an
abnormally high amount of these molecules. He
discussed these findings at the meeting of the Society
for Investigative Dermatology.

"We speculate that people who have rosacea have a
genetically programmed abnormality in their innate
immune system so that these molecules are triggered
too easily. Because of that easy trigger mechanism,
these patients are making too many of these peptides
called cathelicidins," he says.

Dr. Gallo and his co-workers studied 12 rosacea
patients and measured the amount of cathelicidin in
the skin, both the amount of protein and the amount of
messenger RNA. He found that in the case of protein,
there was anywhere between an eight and 15 times
higher amount of cathelicidin in the facial skin from
rosacea patients than in facial skin from normal
patients.

He also wanted to prove that cathelicidin peptides
could cause skin inflammation in mouse skin that looks
like rosacea. When excess cathelicidin was injected
into a mouse, the mouse developed histiocytic
granulomas that resembled rosacea.

Triggers and treatment
One of the triggers for the innate immune system is
infection or bacteria. Rosacea is currently treated
with antibiotics to try to eliminate those bacteria.

"However, the problem may not really be that there are
too many bacteria. The problem may be that the
triggering mechanism is broken," he says.

If this is true, instead of using antibiotics to get
rid of the bacteria, dermatologists could try to fix
the trigger by blocking the easy set point. Dr. Gallo
says that to establish specific treatment, researchers
need to find out more about the triggering system.

"Additionally, if we believe that the disease is
caused by too much cathelicidin, we could develop a
strategy to block the effects of the cathelicidins by
making molecules that mimic that protein but don't
have the same effects," he explains.

Hard way
The current treatment of rosacea works, but the
antibiotics are treating the problem the hard way, he
says. By getting rid of the bacteria, which is the
triggering system, the trigger doesn't get set as
often, so the rosacea will get a little bit better.

"But everybody knows that rosacea patients really
aren't overtly infected. That's not the principal
problem, but there is a way to go before we come up
with an effective strategy that is proven in humans to
block the signaling system," he says.

He noted that biotech companies are developing
effector molecules of the innate immune system and the
natural antimicrobial peptides to attempt to treat
several skin diseases.








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