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المؤلفCampion M.
المؤلفSmith L.
المؤلفGatault S.
المؤلفMétais C.
المؤلفBuddenkotte J.
المؤلفSteinhoff M.
تاريخ الإتاحة2020-04-01T06:54:49Z
تاريخ النشر2019
اسم المنشورExperimental Dermatology
المصدرScopus
الرقم المعياري الدولي للكتاب9066705
معرّف المصادر الموحدhttp://dx.doi.org/10.1111/exd.14034
معرّف المصادر الموحدhttp://hdl.handle.net/10576/13650
الملخصPersistent and relapsing itch commonly manifests in inflammatory skin disorders such as atopic dermatitis (AD). AD pathogenesis is driven by interleukin-4 (IL-4) and interleukin-13 (IL-13). Dupilumab, a monoclonal antibody blocking the action of IL-4 and IL-13 effectively reduces the symptoms of AD and itch. Little is known whether IL-4 and IL-13 directly contribute to itch transduction. A recently published study (Oetjen et al, Cell, 2017, 171, 217) found IL-4 and IL-13 to directly activate itch-sensory neurons in vitro. Surprisingly, they found no significant increase in scratching after intradermally injecting high doses (2.5 ug/ml) of IL-4 and IL-13 into mice. Similar experiments in our lab, however, suggested that both IL-4 and IL-13 contribute to acute itch in vivo. We intradermally injected lower doses (1 ug/ml) of IL-4 and IL-13 into mice and found a significant increase of scratching bouts compared to vehicle. Interestingly, the combined treatment of IL-4 and IL-13 produced additive increase of scratching and acute pruritus at an earlier time point compared to each cytokine administered alone. In summary, our study shows a rapid and significant increase of scratching after intradermal injection of IL-4, IL-13 or combined IL-4/ IL-13 compared to vehicle in mice 5-10 minutes after injection. Our data suggest that IL-4 and IL-13 alone and combined directly act as potent acute pruritogens on sensory nerves. This finding expands our understanding of cytokines as pruritogens, how targeted anticytokine medications act in AD, and about neuroimmune communication in the skin. - 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
راعي المشروعMs Michelle Campion performed the research, analysed the data and wrote the manuscript. Ms Leila Smith and Dr Solène Gatault aided in the research and analysed the data. Dr Charles Métais analysed the data. Dr Buddenkotte aided in the itch mouse model and wrote manuscript. Prof. Dr Dr Martin Steinhoff designed the research study, analysed the data and wrote manuscript. Study was funded by Science Foundation Ireland (IVP award to MS) and Qatar National Research Award (QNRF) (to MS). All authors have read and approved the final manuscript.
اللغةen
الناشرBlackwell Publishing Ltd
الموضوعcytokine
interleukin
itch
pruritus
therapy
العنوانInterleukin-4 and interleukin-13 evoke scratching behaviour in mice
النوعArticle
الصفحات1501-1504
رقم العدد12
رقم المجلد28
dc.accessType Open Access


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