Summary: Researchers have successfully blocked an immune system protein with an antibody to stop itching associated with poison ivy contact.
Strategy could ease itching where steroids, antihistamines are only partly effective.
Scientists at Duke Health and Zhejiang Chinese Medical University have developed a strategy to stop the uncontrollable itch caused by urushiol, the oily sap common to poison ivy, poison sumac, poison oak and even mango trees.
The team found that by blocking an immune system protein in the skin with an antibody, they could halt the processes that tell the brain the skin is itchy. The research was done in mice and is described in the Nov. 7 Proceedings of the National Academy of Sciences. They hope their model could lead to potential treatments for people who are allergic to poison ivy — an estimated 80 percent of the population.
For most people, contact with poisonous plants is painful but not life-threatening. Still, there are significant health care costs associated with more than 10 million people in the U.S. affected each year, said senior author Sven-Eric Jordt, Ph.D., associate professor of anesthesiology at Duke.
“Poison ivy rash is the most common allergic reaction in the U.S., and studies have shown that higher levels of carbon dioxide in the atmosphere are creating a proliferation of poison ivy throughout the U.S. — even in places where it wasn’t growing before,” Jordt said. “When you consider doctor visits, the costs of the drugs that are prescribed and the lost time at work or at school, the societal costs are quite large.”
Some symptoms of the fiery, blistering rash can be alleviated with antihistamines and steroids. But in recent years, scientists have determined that the most severe itching doesn’t go away with antihistamines, because it arises from a different source, Jordt said.
Jordt and collaborators determined the itch is triggered by interleukin 33 (IL-33), a protein in the skin involved in immune response.
All people have IL-33 in their skin, but the protein is elevated in people who have eczema and psoriasis, Jordt said. The protein is known for inducing inflammation, but these new experiments show the protein also acts directly on the nerve fibers in the skin, exciting them and telling the brain that the skin is severely itchy.
The researchers used an antibody to block IL-33 and found that it not only reduced inflammation, but also cut down scratching in mice with poison ivy rashes. An antibody that counteracts human IL-33 is currently being evaluated in humans through a Phase 1 clinical trial to determine its safety and potential side effects.
In an additional approach tested in the mouse experiments, the researchers also found they could also alleviate itch by blocking a receptor for IL-33, called ST2.
“There could be translational significance here,” Jordt said. “So our next step will be to look at human skin to see if we see the same activity and the same pathways. We will also look at anti-inflammatory drugs that are already approved to see if they have the potential to alleviate itch.”
About this neuroscience research article
In addition to Jordt, study authors include Boyi Liu; Yan Tai; Satyanarayana Achanta; Melanie M. Kaelberer; Ana I. Caceres; Xiaomei Shao; and Jianqiao Fang.
Funding: The research was supported by the Duke Anesthesiology DREAM Innovation Grant (2015-DIG LIU), Zhejiang Chinese Medical University Start-Up Funding (722223A08301/ 001/004), the National Natural Science Foundation of China (81603676) and three National Institutes of Health — the National Center for Advancing Translational Sciences (UL1 TR001117), the National Institute of Environmental Health Sciences (R01 ES015056, U01 ES015674) and the National Institute of Arthritis and Musculoskeletal and Skin Disease (R21 AR070554). The authors declare no conflicts of interest.
Source: Samiha Khanna – Duke Image Source: NeuroscienceNews.com image is credited to Sven-Eric Jordt/Duke Health. Original Research:Abstract for “IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy” by Boyi Liu, Yan Tai, Satyanarayana Achanta, Melanie M. Kaelberer, Ana I. Caceres, Xiaomei Shao, Jianqiao Fang, and Sven-Eric Jordt in PNAS. Published online November 7 2016 doi:10.1073/pnas.1606608113
Cite This NeuroscienceNews.com Article
[cbtabs][cbtab title=”MLA”]Duke. “Antibody Can Soothe Raging, Nerve Driven Poison Ivy Itch.” NeuroscienceNews. NeuroscienceNews, 7 November 2016. <https://neurosciencenews.com/poison-ivy-itch-antibody-5452/>.[/cbtab][cbtab title=”APA”]Duke. (2016, November 7). Antibody Can Soothe Raging, Nerve Driven Poison Ivy Itch. NeuroscienceNews. Retrieved November 7, 2016 from https://neurosciencenews.com/poison-ivy-itch-antibody-5452/[/cbtab][cbtab title=”Chicago”]Duke. “Antibody Can Soothe Raging, Nerve Driven Poison Ivy Itch.” https://neurosciencenews.com/poison-ivy-itch-antibody-5452/ (accessed November 7, 2016).[/cbtab][/cbtabs]
IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy
Poison ivy-induced allergic contact dermatitis (ACD) is the most common environmental allergic condition in the United States. Case numbers of poison ivy ACD are increasing due to growing biomass and geographical expansion of poison ivy and increasing content of the allergen, urushiol, likely attributable to rising atmospheric CO2. Severe and treatment-resistant itch is the major complaint of affected patients. However, because of limited clinical data and poorly characterized models, the pruritic mechanisms in poison ivy ACD remain unknown. Here, we aim to identify the mechanisms of itch in a mouse model of poison ivy ACD by transcriptomics, neuronal imaging, and behavioral analysis. Using transcriptome microarray analysis, we identified IL-33 as a key cytokine up-regulated in the inflamed skin of urushiol-challenged mice. We further found that the IL-33 receptor, ST2, is expressed in small to medium-sized dorsal root ganglion (DRG) neurons, including neurons that innervate the skin. IL-33 induces Ca2+ influx into a subset of DRG neurons through neuronal ST2. Neutralizing antibodies against IL-33 or ST2 reduced scratching behavior and skin inflammation in urushiol-challenged mice. Injection of IL-33 into urushiol-challenged skin rapidly exacerbated itch-related scratching via ST2, in a histamine-independent manner. Targeted silencing of neuronal ST2 expression by intrathecal ST2 siRNA delivery significantly attenuated pruritic responses caused by urushiol-induced ACD. These results indicate that IL-33/ST2 signaling is functionally present in primary sensory neurons and contributes to pruritus in poison ivy ACD. Blocking IL-33/ST2 signaling may represent a therapeutic approach to ameliorate itch and skin inflammation related to poison ivy ACD.
“IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy” by Boyi Liu, Yan Tai, Satyanarayana Achanta, Melanie M. Kaelberer, Ana I. Caceres, Xiaomei Shao, Jianqiao Fang, and Sven-Eric Jordt in PNAS. Published online November 7 2016 doi:10.1073/pnas.1606608113