Feeling Itchy and Scratchy? New Study Finds the Unexpected Solution to Your Persistent Itch – and Here’s What You Need to Know

While scratching an itch can provide temporary relief, persistent itching can signify more serious health concerns. But what signals our body to halt the itching?

Researchers at UC San Francisco are edging towards unraveling this mystery. Their pioneering research has identified a unique mechanism involving an immune protein, IL-31. This protein not only instigates the sensation of itching but also moderates surrounding inflammation.

The study, unveiled today in Science Immunology, sets the stage for the development of next-gen medications that harmonize seamlessly with the body’s inherent regulatory functions.

Earlier theories posited IL-31 as a mere agent signaling itchiness and inciting skin inflammation. However, UCSF’s revelation indicates that nerve cells (neurons) reacting to IL-31 not only provoke scratching but also inhibit immune cells from extreme reactions that lead to broader inflammation.

Dr. Marlys Fassett, UCSF’s dermatology professor and the study’s main contributor, highlighted, “We tend to think that immune proteins like IL-31 help immune cells talk to one another, but here, when IL-31 talks to neurons, the neurons talk right back.”

The expert emphasized: “It’s the first time we’ve seen the nervous system directly tamp down an allergic response.”  

This groundbreaking insight holds the potential to revolutionize treatments for conditions like asthma and Crohn’s, given the widespread presence of IL-31 in our bodies.

Emphasizing its prevalence, Dr. Mark Ansel, a distinguished professor of immunology at UCSF and the study’s senior researcher, stated, “IL-31 causes itch in the skin, but it’s also in the lung and in the gut. We now have a new lead for fighting the many diseases involving both the immune and nervous systems.”

Beyond Just an Itch

IL-31 stands out among a group of itch-inducing cytokines due to its pronounced effect on triggering itchiness in both animals and humans. Ever since joining UCSF in 2012, Fassett, with her dual expertise as a dermatologist and researcher, has been intrigued by the workings of IL-31, especially since its identification a few years prior. Her curiosity led her to collaborate with Ansel, a past associate and an authority on asthma, in his research facility.

In one of their key experiments, Fassett eliminated the IL-31 gene from mice and introduced them to the house dust mite, a prevalent allergen known to cause itchiness.

“We wanted to mimic what was actually happening in people who are chronically exposed to environmental allergens,” explained Fassett. “As we expected, the dust mite didn’t cause itching in the absence of IL-31, but we were surprised to see that inflammation went up

But why the rise in inflammation without the itch? The duo deduced that in the absence of this specific itch-triggering cytokine, the body’s immune cells had become hyperactive. It seemed that without IL-31, the body was inadvertently escalating its immune response.

Harmonizing the Body’s Responses

Diving deeper into their research, Ansel and Fassett pinpointed specific nerve cells in the skin that interacted with the IL-31 molecule. They identified that these very nerve cells, which initiate the scratching reflex, also play a role in tempering the subsequent immune activity. Without IL-31, however, these nerve cells seem to lose their restraining influence, allowing the immune response to go unchecked.

This observation was consistent with the effects noticed by skin specialists when using a recently introduced drug, nemolizumab. This drug, which inhibits IL-31 and is intended for eczema treatment, showed promising results in diminishing the classic dry and patchy skin symptoms of eczema. Yet, some patients reported other skin complications and occasional inflammation in respiratory regions.

Ansel remarked, “When you give a drug that blocks the IL-31 receptor throughout the whole body, now you’re changing that feedback system, releasing the brakes on allergic reactions everywhere.”

Furthering their investigation, the duo observed that these particular nerve cells emitted a distinct signal, labeled as CGRP, when prompted by the itch stimulus. This signal might be the factor counteracting the immune overdrive.

“The idea that our nerves contribute to allergy in different tissues is game changing,” commented Fassett. “If we can develop drugs that work around these systems, we can really help those patients that get worse flares after treatment for itch.”

Having established her own research space at UCSF, Fassett is eager to unravel these intriguing biological contradictions that influence therapeutic success. Ansel, on the other hand, is curious about IL-31’s role beyond dermatological aspects.

Ansel pondered, “You don’t itch in your lungs, so the question is, what is IL-31 doing there, or in the gut?

“But it does seem to have an effect on allergic inflammation in the lung. There’s a lot of science ahead for us, with immense potential to improve therapies.”

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