Interleukin 31 mediates pruritus in horses.
Abstract: 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. Conclusions: Interleukin 31 is a promising therapeutic target for equine allergic pruritus.
Publication Date: 2024-10-14 PubMed ID: 39406262DOI: 10.2460/ajvr.24.05.0144Google Scholar: Lookup
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Summary
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This study explores the influence of Interleukin 31 (IL-31) on itchiness (pruritus) in horses and suggests it as a potential therapeutic target for equine allergic itchiness.
Research Methodology
- Being a part of the study, the researchers first confirmed the sequences of equine IL-31 mRNA via sequencing.
- A recombinant variant of eIL-31 was manufactured using both mammalian and bacterial expression systems. Recombinant refers to any DNA formed through laboratory methods rather than occurring naturally.
- For over a year (November 2019 – February 2021), 12 healthy horses of ages between 6 and 10 years having no previous history of allergic skin disease were injected IntraDermally (ID) with either eIL-31 and saline in two separate challenge studies.
- Pruritus-associated behaviors were tracked and recorded for at least 15 minutes before the injection and for 4 hours post the injection.
- Monocytes, a type of white blood cell, from 3 horses showing pruritus symptoms and suffering from insect bite hypersensitivity and/or atopic dermatitis, were induced with bacterial eIL-31 resulting in an increased phosphorylation of signal transducer and activator of transcription 3 (STAT3). The measurement for this was taken using techniques such as western blot and AlphaLISA.
Research Findings
- The eIL-31 resulted in higher purity when produced in a bacterial system compared to a mammalian system, as indicated by purity percentages (95% vs 70%).
- Pruritus (itching behavior) was noticed with the injection of both forms of eIL-31. Injections using mammalian eIL-31 resulted in mild pruritus, while the bacterial eIL-31 induced marked pruritus in some horses and a milder response in others.
- The majority of the pruritus (itching behavior) was observed to occur after two hours post the injection, and then started to subside by 4 hours post-injection.
- The bacterial version of eIL-31 prompted the phosphorylation of STAT3 within the monocytes of allergic horses. Phosphorylation of STAT3 is a cellular process to regulate cell growth and division, and increased phosphorylation could indicate cellular changes due to eIL-31 stimulation.
Research Conclusion
- This study provides proof-of-concept evidence that IL-31 mediates, or is a potential cause of, pruritus and is associated with STAT3 phosphorylation in horses, similar to other species.
- The findings imply that Interleukin 31 is a promising target for therapeutic methods intended to treat equine allergic pruritus.
Cite This Article
APA
Craig NM, Munguia NS, Trujillo AD, Chan AM, Wilkes R, Dorr M, Marsella R.
(2024).
Interleukin 31 mediates pruritus in horses.
Am J Vet Res, 1-11.
https://doi.org/10.2460/ajvr.24.05.0144 Publication
Researcher Affiliations
- College of Veterinary Medicine, University of Florida, Gainesville, FL.
- Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK.
- College of Veterinary Medicine, University of Florida, Gainesville, FL.
- College of Veterinary Medicine, University of Florida, Gainesville, FL.
- College of Veterinary Medicine, University of Florida, Gainesville, FL.
- College of Veterinary Medicine, University of Florida, Gainesville, FL.
- College of Veterinary Medicine, University of Florida, Gainesville, FL.
- Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK.
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