评估一次性口服奥克拉替尼对健康犬皮内白介素-31致瘙痒注射(“反应性”模型)后瘙痒行为的影响:一项盲法、随机、交叉研究。

IF 1.4 3区 农林科学 Q3 DERMATOLOGY
Renato Leon, Haley Starr, Frane Banovic
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引用次数: 0

摘要

背景:在临床前药物试验中,健康犬被应用白细胞介素(IL)-31,通过“预防性”设计方法(即在IL-31给药之前给药)来评估新型药物的止痒效果。假设/目标:通过口服奥克拉西替尼,在健康狗身上建立并验证“反应性”皮内il -31诱导的瘙痒模型。动物:8只健康的成年比格犬。材料和方法:一项盲法、随机交叉研究。所有的狗都接受皮内重组犬IL-31,同时或不给予单剂量口服奥拉西替尼;在洗脱期4周后进行交叉治疗。结果:奥拉西替尼减轻了皮内注射IL-31后总瘙痒行为(p = 0.0252)和局部瘙痒行为(p = 0.0078)。它还减少了抓挠(p = 0.0078),咀嚼/咬(p = 0.0078)和摇头(p = 0.0255)行为的总秒数。舔的次数没有明显减少。在这种“反应性”模型中,奥克拉替尼在120-180分钟(p = 0.0058)、180-240分钟(p = 0.0075)和240-300分钟(p = 0.0241)时观察到总瘙痒秒的减少。同样,局部瘙痒行为秒在60-120分钟(p = 0.0498)和240-300分钟(p = 0.0343)时也有所减少。结论及临床意义:本研究首次在健康犬身上建立了“反应性”犬皮内IL-31瘙痒模型。一次性口服奥克拉西替尼可显著降低瘙痒行为的发生率。在未来的临床前试验中,新型止痒药物可以使用这种“反应性”模型进行评估和比较。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of One-Time Oral Oclacitinib Administration on Pruritic Behaviours After Intradermal Interleukin-31-Induced Pruritus Injections ("Reactive" Model) in Healthy Dogs: A Blinded, Randomised, Cross-Over Study.

Background: Administration of interleukin (IL)-31 to healthy dogs has been used in preclinical drug testing to evaluate the antipruritic effect of novel medications through a "preventative" design approach (i.e., drugs are given before IL-31 administration).

Hypothesis/objectives: Develop and validate a "reactive" intradermal IL-31-induced pruritus model in healthy dogs by administering oral oclacitinib.

Animals: Eight adult, healthy research-bred beagles.

Materials and methods: A blinded, randomised, cross-over study. All dogs received either intradermal recombinant canine IL-31 with or without a single dose of oral oclacitinib given afterward; cross-over treatment was administered following a 4-week washout period.

Results: Oclacitinib reduced the total (p = 0.0252) and local (p = 0.0078) pruritic behaviour seconds after intradermal IL-31 injections. It also reduced the total seconds of scratching (p = 0.0078), chewing/biting (p = 0.0078) and head-shaking (p = 0.0255) behaviours. No significant reduction in licking was observed. Decreases in total pruritic seconds in this "reactive" model following oclacitinib administration were observed at 120-180 min (p = 0.0058), 180-240 min (p = 0.0075) and 240-300 min (p = 0.0241). Likewise, decreases in local pruritic behaviour seconds were observed at 60-120 min (p = 0.0498) and 240-300 min (p = 0.0343).

Conclusions and clinical relevance: The study established the first "reactive" canine intradermal IL-31 itch model in healthy dogs. One-time oral administration of oclacitinib significantly reduced the incidence of pruritic behaviours. Novel antipruritic medications can be assessed and compared using this "reactive" model in future preclinical trials.

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来源期刊
Veterinary dermatology
Veterinary dermatology 农林科学-兽医学
CiteScore
3.20
自引率
21.40%
发文量
92
审稿时长
12-24 weeks
期刊介绍: Veterinary Dermatology is a bi-monthly, peer-reviewed, international journal which publishes papers on all aspects of the skin of mammals, birds, reptiles, amphibians and fish. Scientific research papers, clinical case reports and reviews covering the following aspects of dermatology will be considered for publication: -Skin structure (anatomy, histology, ultrastructure) -Skin function (physiology, biochemistry, pharmacology, immunology, genetics) -Skin microbiology and parasitology -Dermatopathology -Pathogenesis, diagnosis and treatment of skin diseases -New disease entities
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