Department of Clinical Sciences, College of Veterinary Medicine, NC State University, Raleigh, North Carolina, USA.
Veterinary Medicine Research & Development, Zoetis Inc., Fort Collins, Colorado, USA.
Vet Dermatol. 2023 Aug;34(4):327-338. doi: 10.1111/vde.13159. Epub 2023 Apr 2.
The caninised monoclonal antibody lokivetmab (LKV), directed at interleukin (IL)-31, is very effective at controlling pruritus in most dogs with atopic dermatitis (AD). However, evidence exists that IL-31 is not required for the induction of acute allergic skin inflammation, which might explain why this treatment is less efficacious in some dogs with AD.
HYPOTHESIS/OBJECTIVES: To compare the comprehensive transcriptome analysis of house dust mite (HDM)-sensitised dogs with and without treatment with LKV to attest our hypothesis that LKV does not majorly affect acute cytokine/chemokine production.
Six HDM-sensitised atopic Maltese-beagle dogs.
In this cross-over study, the cytokine profiling of acute AD skin lesions was compared by RNA sequencing (RNA-Seq), with or without LKV-induced inhibition of IL-31. Skin biopsies were obtained from each dog at 0, 6, 12, 24, 48, and 96 h after epicutaneous HDM allergen provocation.
Macroscopic and microscopic skin lesion scores were not significantly different between the LKV- and nontreatment groups at any time points. Likewise, the results of RNA-Seq analysis revealed no significant difference in the messenger (m)RNA expression of the major cytokines between these two groups. In LKV-treated dogs, IL6, IL9, IL13, IL33, CCL17, and CCL22 were significantly upregulated compared to their baseline expression levels, suggesting that these cytokines are unaffected by IL-31 inhibition.
IL-31 inhibition is insufficient to prevent the expression of other proinflammatory mediators in acute AD and these could be considered as other potential therapeutic targets.
犬源化单克隆抗体洛匹那韦（LKV）针对白细胞介素（IL）-31，对大多数特应性皮炎（AD）犬的瘙痒非常有效。然而，有证据表明，IL-31 并非诱导急性过敏皮肤炎症所必需，这可能解释了为什么这种治疗对某些 AD 犬的疗效较差。
假设/目的：比较屋尘螨（HDM）致敏犬接受和未接受 LKV 治疗的综合转录组分析，以验证我们的假设，即 LKV 不会主要影响急性细胞因子/趋化因子的产生。
6 只 HDM 致敏的特应性马尔济斯-比格犬。
在这项交叉研究中，通过 RNA 测序（RNA-Seq）比较急性 AD 皮肤病变的细胞因子谱，同时比较有无 LKV 抑制 IL-31。在经皮 HDM 过敏原激发后 0、6、12、24、48 和 96 h，从每只狗身上获取皮肤活检。
在任何时间点，LKV 治疗组和未治疗组的宏观和微观皮肤病变评分均无显著差异。同样，RNA-Seq 分析结果也表明，这两组之间主要细胞因子的信使（m）RNA 表达没有显著差异。在 LKV 治疗犬中，与基线表达水平相比，IL6、IL9、IL13、IL33、CCL17 和 CCL22 的表达显著上调，这表明这些细胞因子不受 IL-31 抑制的影响。
IL-31 抑制不足以防止急性 AD 中其他促炎介质的表达，这些介质可能被视为其他潜在的治疗靶点。
