Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis
Pruritic models in healthy dogs utilizing intravenous administration of interleukin 31 (IL-31) bypass the “natural” itch sensation in AD, which is initiated by pruriceptive primary afferent neurons in the skin. This study aimed to evaluate the immediate/delayed pruritus responses and the pruritic be...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Veterinary Sciences |
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| Online Access: | https://www.mdpi.com/2306-7381/10/5/329 |
| _version_ | 1797598121029533696 |
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| author | Jason Pearson Renato Leon Haley Starr Sujung Jun Kim Jonathan E. Fogle Frane Banovic |
| author_facet | Jason Pearson Renato Leon Haley Starr Sujung Jun Kim Jonathan E. Fogle Frane Banovic |
| author_sort | Jason Pearson |
| collection | DOAJ |
| description | Pruritic models in healthy dogs utilizing intravenous administration of interleukin 31 (IL-31) bypass the “natural” itch sensation in AD, which is initiated by pruriceptive primary afferent neurons in the skin. This study aimed to evaluate the immediate/delayed pruritus responses and the pruritic behaviors observed in an intradermal IL-31-induced pruritic model of healthy dogs and the anti-pruritic effect of oclacitinib on said model. In Phase 1, all the dogs were randomized and video-recorded for 300 min after intradermal canine recombinant IL-31 injections (1.75 µg/kg) and vehicle (phosphate-buffered saline) injections. In Phase 2, all the dogs received oral oclacitinib (0.4–0.6 mg/kg, twice daily for 4 consecutive days and once daily on day 5), with the intradermal IL-31 injection performed on day 5. Two blinded investigators reviewed the pruritic behaviors in all the video recordings. Intradermal IL-31 administration to healthy dogs caused a significant increase in the total (<i>p</i> = 0.0052) and local (<i>p</i> = 0.0003) seconds of pruritic behavior compared to the vehicle control. Oral oclacitinib administration significantly reduced the total (<i>p</i> = 0.0011) and local (<i>p</i> = 0.0156) intradermal IL-31-induced pruritic seconds; there was no significant difference in pruritic seconds between the vehicle and oclacitinib within the IL-31 groups. Significant delayed pruritic responses at 150–300 min after IL-31 injections were observed, and intradermal IL-31 failed to induce acute itch (first 30 min). Intradermal injection of IL-31 induces delayed itch responses in dogs that are diminished by the effect of oclacitinib, an oral JAK inhibitor. |
| first_indexed | 2024-03-11T03:14:51Z |
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| institution | Directory Open Access Journal |
| issn | 2306-7381 |
| language | English |
| last_indexed | 2024-03-11T03:14:51Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Veterinary Sciences |
| spelling | doaj.art-dcf3b502f7f54cf4a4966b40aea2e6cf2023-11-18T03:37:23ZengMDPI AGVeterinary Sciences2306-73812023-05-0110532910.3390/vetsci10050329Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic DermatitisJason Pearson0Renato Leon1Haley Starr2Sujung Jun Kim3Jonathan E. Fogle4Frane Banovic5College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USACollege of Veterinary Medicine, University of Georgia, Athens, GA 30602, USACollege of Veterinary Medicine, University of Georgia, Athens, GA 30602, USABoehringer Ingelheim Animal Health, Athens, GA 30601, USABoehringer Ingelheim Animal Health, Athens, GA 30601, USACollege of Veterinary Medicine, University of Georgia, Athens, GA 30602, USAPruritic models in healthy dogs utilizing intravenous administration of interleukin 31 (IL-31) bypass the “natural” itch sensation in AD, which is initiated by pruriceptive primary afferent neurons in the skin. This study aimed to evaluate the immediate/delayed pruritus responses and the pruritic behaviors observed in an intradermal IL-31-induced pruritic model of healthy dogs and the anti-pruritic effect of oclacitinib on said model. In Phase 1, all the dogs were randomized and video-recorded for 300 min after intradermal canine recombinant IL-31 injections (1.75 µg/kg) and vehicle (phosphate-buffered saline) injections. In Phase 2, all the dogs received oral oclacitinib (0.4–0.6 mg/kg, twice daily for 4 consecutive days and once daily on day 5), with the intradermal IL-31 injection performed on day 5. Two blinded investigators reviewed the pruritic behaviors in all the video recordings. Intradermal IL-31 administration to healthy dogs caused a significant increase in the total (<i>p</i> = 0.0052) and local (<i>p</i> = 0.0003) seconds of pruritic behavior compared to the vehicle control. Oral oclacitinib administration significantly reduced the total (<i>p</i> = 0.0011) and local (<i>p</i> = 0.0156) intradermal IL-31-induced pruritic seconds; there was no significant difference in pruritic seconds between the vehicle and oclacitinib within the IL-31 groups. Significant delayed pruritic responses at 150–300 min after IL-31 injections were observed, and intradermal IL-31 failed to induce acute itch (first 30 min). Intradermal injection of IL-31 induces delayed itch responses in dogs that are diminished by the effect of oclacitinib, an oral JAK inhibitor.https://www.mdpi.com/2306-7381/10/5/329caninepruritusinterleukin-31atopic dermatitisoclacitinib |
| spellingShingle | Jason Pearson Renato Leon Haley Starr Sujung Jun Kim Jonathan E. Fogle Frane Banovic Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis Veterinary Sciences canine pruritus interleukin-31 atopic dermatitis oclacitinib |
| title | Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis |
| title_full | Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis |
| title_fullStr | Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis |
| title_full_unstemmed | Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis |
| title_short | Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis |
| title_sort | establishment of an intradermal canine il 31 induced pruritus model to evaluate therapeutic candidates in atopic dermatitis |
| topic | canine pruritus interleukin-31 atopic dermatitis oclacitinib |
| url | https://www.mdpi.com/2306-7381/10/5/329 |
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