June 2015

Listening to the ‘conversations’ behind itch and rosacea

Fri, 5 June 15 16:05

Skin conditions often run deeper than you might think. The itch of eczema or the flushing of rosacea owe much to a complex ‘conversation’ of molecular signals within the body, and Professor Martin Steinhoff is on a mission to better understand and block the chemical cascades that can lead to irritating or socially embarrassing symptoms.

Scratching for answers

Chronic itch can be a problematic symptom of various conditions, including atopic dermatitis (eczema), psoriasis, liver and kidney diseases and leukemia. “This itch can be debilitating, it can interfere with sleep meaning that people cannot function the next day, it makes people irritable, aggressive,” says Charles Institute Director Professor Steinhoff, professor of dermatology at UCD. “But unlike, say, chronic pain, where you have different types of therapies for different types of pain, at the moment the treatment options for different types of itch are not well defined, and we need to find more specific ways to treat them.”

Professor Steinhoff is interested in finding out how cells and molecules ‘talk’ to each other in the skin to trigger itch in different sub-types of patients. The histamine molecule is a key player here, but several years ago while at the University of San Francisco, Professor Steinhoff and colleagues discovered a new mechanism by which the the immune system, which is responsible for inflammation in the skin, talks to the nervous system, which conveys messages to and from the brain. “We revealed this new histamine-independent mechanism, where enzymes called proteases are released from immune cells and can talk to sensory nerves in a way that not only induces inflammation but also itch,” he explains.

Since then, Professor Steinhoff has made several more discoveries about how chemical messengers, and particularly the short-range messengers known as cytokines and chemokines, relay ‘itch’ signals in the skin and couple the immune and nervous systems. He is now working on a Science Foundation Ireland Investigator Programme to explore these itch pathways in various types of skin conditions and other diseases, and the hope is to find new targets that can stop the itch. “We want to define these pathways to find the mediators and the receptors that are involved in this itch transmission to the central nervous system,” he explains. “Then we want to develop new drugs for the treatment of pruritic (itch) symptoms based on molecules that block these cytokine and chemokine pathways.”

Seeing red

It’s not just itch that involves the interplay of systems in the body - in rosacea too the typical flushing or redness of the face develops from cross-talk between the nervous, immune and cardiovascular systems, as Professor Steinhoff explains. “The communication between immune cells and blood vessels and nerves can lead to the red face, which is a typical characteristic of a rosacea patient,” he says. ‘So typically there is Immediate flushing perhaps after eating spicy food, drinking red wine, going out into the sun or exercising and this flushing is regulated by the nervous system, which leads to prolonged and increased blood flow to the skin, and there is also communication with immune cells which then results in chronic inflammation. This interaction between the three systems is probably the key to understand the pathophysiology of rosacea.”

Again Professor Steinhoff is teasing out the roles of individual molecules and pathways in this chain of events, with a view to developing new treatments. “You need to block not only the expansion of the blood vessels, you also need to stop the nerves talking to the immune cells in order to control the inflammation,” he says.

Fascinating organ

The skin has long intrigued Professor Steinhoff, who studied medicine in Marburg, Germany, and was interested in how often the dermatology textbooks often said the origin of skin conditions was unknown. “I thought there had to be a lot of discoveries to be made there,” he recalls. “Also the skin has such a variety of functions - it is our first border to the environment, it is involved in emotional sensing and communication, there is an aesthetic component, it has several physiological roles and also then disruption of the skin is involved in so many diseases. It is a fascinating organ.”

(In conversation with freelance journalist, Claire O'Connell) 

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