Preparation of anti-canine interleukin-31 receptor alpha polyclonal antibody and evaluation of its therapeutic effect in canine atopic dermatitis

Canine atopic dermatitis (CAD) is a prevalent genetically susceptible inflammatory and pruritic allergic skin condition affecting not only the health of dogs but also the quality of life of their owners. Interleukin-31 (IL-31) and interleukin-31 receptor alpha (IL-31RA) are essential for the development of pruritus in primates and mice. Hence, it is expected that inhibiting IL-31RA will be an effective approach to alleviate pruritus. The purpose of the study was to produce anti-canine IL-31RA polyclonal antibodies (anti-IL-31RA pAbs) and evaluate their efficacy in inhibiting house dust mite (HDM)-evoked pruritic responses. Dogs were immunized with antigens formed by IL-31RA recombinant short peptides coupled to BSA to produce anti-IL-31RA pAbs. The CAD model was developed by using HDM allergen stimulation, and the effects of IL-31RA pAbs on the reduction of pruritus in CAD model dogs were examined. The Canine Atopic Dermatitis Extent and Severity Index (CADESI)-4 and pruritus Visual Analog Scale (pVAS) were utilized to evaluate pruritic responses, and skin tissue samples were collected from the inguinal area for pathological assessment of skin inflammatory cell infiltration. The results showed that anti-IL-31RA pAbs with high titers (1:128,000) and specificity were effectively produced. In the CAD model group, the severity of skin damage, pruritus score, inflammatory cell infiltration and level of inflammatory factors were considerably elevated. Anti-IL-31RA pAbs relieved pruritic behavior and dermatitis in dogs compared to placebo-treated dogs. In conclusion, anti-IL-31RA pAbs effectively suppressed CAD in vivo and are anticipated to be an effective novel treatment for pruritic skin disorders such as CAD.