Pearson Jason, Leon Renato, Starr Haley, Kim Sujung Jun, Fogle Jonathan E, Banovic Frane
College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Boehringer Ingelheim Animal Health, Athens, GA 30601, USA.
Vet Sci. 2023 May 4;10(5):329. doi: 10.3390/vetsci10050329.
Pruritic models in healthy dogs utilizing intravenous administration of interleukin 31 (IL-31) bypass the "natural" itch sensation in AD, which is initiated by pruriceptive primary afferent neurons in the skin. This study aimed to evaluate the immediate/delayed pruritus responses and the pruritic behaviors observed in an intradermal IL-31-induced pruritic model of healthy dogs and the anti-pruritic effect of oclacitinib on said model. In Phase 1, all the dogs were randomized and video-recorded for 300 min after intradermal canine recombinant IL-31 injections (1.75 µg/kg) and vehicle (phosphate-buffered saline) injections. In Phase 2, all the dogs received oral oclacitinib (0.4-0.6 mg/kg, twice daily for 4 consecutive days and once daily on day 5), with the intradermal IL-31 injection performed on day 5. Two blinded investigators reviewed the pruritic behaviors in all the video recordings. Intradermal IL-31 administration to healthy dogs caused a significant increase in the total ( = 0.0052) and local ( = 0.0003) seconds of pruritic behavior compared to the vehicle control. Oral oclacitinib administration significantly reduced the total ( = 0.0011) and local ( = 0.0156) intradermal IL-31-induced pruritic seconds; there was no significant difference in pruritic seconds between the vehicle and oclacitinib within the IL-31 groups. Significant delayed pruritic responses at 150-300 min after IL-31 injections were observed, and intradermal IL-31 failed to induce acute itch (first 30 min). Intradermal injection of IL-31 induces delayed itch responses in dogs that are diminished by the effect of oclacitinib, an oral JAK inhibitor.
在健康犬中使用静脉注射白细胞介素31(IL-31)的瘙痒模型绕过了特应性皮炎(AD)中由皮肤内瘙痒感受性初级传入神经元引发的“自然”瘙痒感觉。本研究旨在评估在健康犬的皮内注射IL-31诱导的瘙痒模型中观察到的即时/延迟瘙痒反应和瘙痒行为,以及奥克拉替尼对该模型的止痒效果。在第1阶段,所有犬只在皮内注射犬重组IL-31(1.75μg/kg)和赋形剂(磷酸盐缓冲盐水)后随机分组并进行300分钟的视频记录。在第2阶段,所有犬只口服奥克拉替尼(0.4 - 0.6mg/kg,连续4天每日两次,第5天每日一次),并在第5天进行皮内IL-31注射。两名盲法研究者审查了所有视频记录中的瘙痒行为。与赋形剂对照组相比,对健康犬进行皮内注射IL-31导致瘙痒行为的总时长(P = 0.0052)和局部时长(P = 0.0003)显著增加。口服奥克拉替尼显著减少了皮内注射IL-31诱导的瘙痒总时长(P = 0.0011)和局部时长(P = 0.0156);在IL-31组中,赋形剂和奥克拉替尼之间的瘙痒时长无显著差异。在注射IL-31后150 - 300分钟观察到显著的延迟瘙痒反应,皮内注射IL-31未能诱导急性瘙痒(最初30分钟)。皮内注射IL-31在犬中诱导延迟瘙痒反应,该反应可被口服JAK抑制剂奥克拉替尼的作用所减轻。