1. Interleukin 31 mediates pruritus in horses.
- Author
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Craig NM, Munguia NS, Trujillo AD, Chan AM, Wilkes R, Dorr M, and Marsella R
- Subjects
- Animals, Horses, Male, Female, Phosphorylation, Monocytes metabolism, Monocytes drug effects, Pruritus veterinary, Interleukins genetics, Interleukins metabolism, Horse Diseases, Recombinant Proteins
- Abstract
Objective: This study investigated the effects of recombinant equine IL-31 (eIL-31) in vivo and in vitro., Methods: Equine IL-31 mRNA sequences were verified by sequencing. Recombinant eIL-31 was produced using mammalian and bacterial expression systems. From November 2019 through February 2021, 12 normal horses, 6 to 10 years old with no history or clinical signs consistent with allergic skin disease, were injected ID with eIL-31 and saline in 2 challenge studies. Pruritus-associated behaviors were recorded for a minimum of 15 minutes preinjection and 4 hours postinjection. Adherent monocytes from 3 pruritic horses, exhibiting insect bite hypersensitivity and/or atopic dermatitis, were stimulated with bacterial eIL-31, and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) was measured by western blot and AlphaLISA., Results: The bacterial eIL-31 was produced with greater purity than the mammalian eIL-31 (> 95% vs 70%). Pruritus was elicited by both recombinant proteins. The mammalian eIL-31 induced mild pruritus (cumulative seconds spent itching postinjection ranged from 6 to 313). The bacterial eIL-31 induced marked pruritus in some horses (a cumulative maximum of 5,529 seconds spent itching in 1 horse) and a milder response in others (range of cumulative seconds spent itching, 17 to 2,313). Most pruritus occurred after 2 hours and subsided by 4 hours postinjection. Bacterial eIL-31 induced STAT3 phosphorylation in adherent monocytes from allergic horses., Conclusions: In this proof-of-concept study, IL-31 was found to mediate pruritus and was associated with STAT3 phosphorylation in horses as in other species., Clinical Relevance: Interleukin 31 is a promising therapeutic target for equine allergic pruritus.
- Published
- 2024
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