Work

Cytokine transcriptome profiling in acute experimental canine atopic dermatitis skin lesions after IL ‐31 inhibition with lokivetmab

Year: 2023

Type: article

Abstract: BACKGROUND: 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. ANIMALS: Six HDM-sensitised atopic Maltese-beagle dogs. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.

Source: Veterinary Dermatology

DOI: 10.1111/vde.13159

Authors: Chie Tamamoto‐Mochizuki, Natalie Crawford, Jordan M. Eder, Andrea J. Gonzales, Thierry Olivry

Institutions: North Carolina State University, Zoetis (United States)

Language: English

Topic: Dermatology and Skin Diseases

Subfield: Dermatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,400