{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T18:32:40Z","timestamp":1777573960907,"version":"3.51.4"},"reference-count":14,"publisher":"American Veterinary Medical Association (AVMA)","issue":"12","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>To perform testing for cytokines involved in dermal inflammatory reactions and to document and compare the effects of an oleander extract (OE), oleandrin, and oclacitinib on biomarkers relevant to allergic reactions. The effects of these compounds under inflamed culture conditions are of direct importance to the treatment of canine atopic dermatitis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>METHODS<\/jats:title>\n<jats:p>Testing involved primary canine dermal fibroblasts and the canine DH82 macrophage cell line; both cell types are important for initiating, regulating, and resolving dermal allergic reactions via cytokine communication.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>RESULTS<\/jats:title>\n<jats:p>Under inflamed conditions, OE and oleandrin downregulated key cytokines secreted by canine dermal fibroblasts and the DH82 macrophage cell line; all of which are treatment targets in dermatitis. In the DH82 macrophage cultures, the most noteworthy reductions involved IL-6, IL-12\/IL-23p40, interferon-\u03b3, tumor necrosis factor-\u03b1, VEGF, and nerve growth factor-\u03b2. Oclacitinib triggered reductions of some cytokines involved in allergic reactions, including TGF-\u03b21, IL-12\/IL-23p40, and tumor necrosis factor-\u03b1; however, these reductions were less robust than the reductions triggered by OE and oleandrin and accompanied by increases in other cytokines involved in dermal inflammation, including IL-6, interferon-\u03b3, and nerve growth factor-\u03b2. In cultures of primary dermal fibroblasts, OE and oleandrin reduced the levels of IL-8 and monocyte chemoattractant protein-1, whereas oclacitinib had little or no effect.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>Oleander extract and oleandrin directly modulate immune responses under inflamed conditions. Moreover, OE and oleandrin appear to provide a more beneficial overall cytokine regulation than oclacitinib under inflamed culture conditions.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>CLINICAL RELEVANCE<\/jats:title>\n<jats:p>These results suggest that OE and oleandrin are efficacious agents to treat canine atopic dermatitis. Future studies should evaluate the efficacy of these compounds in dogs affected by atopic dermatitis.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.24.05.0153","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T14:48:12Z","timestamp":1727966892000},"source":"Crossref","is-referenced-by-count":1,"title":["Botanical oleander extract and oleandrin have superior effects on innate immune functions pertaining to dermal allergic reactions in canine cells when compared to oclacitinib"],"prefix":"10.2460","volume":"85","author":[{"given":"Theresa W.","family":"Fossum","sequence":"first","affiliation":[{"name":"Phoenix Animal Wellness, San Antonio, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gitte S.","family":"Jensen","sequence":"additional","affiliation":[{"name":"NIS Labs, Klamath Falls, OR"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Newman","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center, University of Texas, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose R.","family":"Matos","sequence":"additional","affiliation":[{"name":"Innovar LLC, Plano, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"issue":"3","key":"B1","series-title":"J Pharmacol Exp Ther","first-page":"394","article-title":"Topically administered janus-kinase inhibitors tofacitinib and oclacitinib display impressive antipruritic and anti-inflammatory responses in a model of allergic dermatitis","volume":"354","author":"Fukuyama T","year":"2015","unstructured":"Fukuyama T, Ehling S, Cook E, B\u00e4umer W. Topically administered janus-kinase inhibitors tofacitinib and oclacitinib display impressive antipruritic and anti-inflammatory responses in a model of allergic dermatitis. J Pharmacol Exp Ther. 2015;354(3):394\u2013405. doi:10.1124\/jpet.115.223784"},{"issue":"1","key":"B2","series-title":"Vet Dermatol","first-page":"17-e6","article-title":"Immunomodulatory in vitro effects of oclacitinib on canine T-cell proliferation and cytokine production","volume":"30","author":"Banovic F","year":"2019","unstructured":"Banovic F, Tarigo J, Gordon H, Barber JP, Gogal RM Jr. Immunomodulatory in vitro effects of oclacitinib on canine T-cell proliferation and cytokine production. 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Differential activities of the botanical extract PBI-05204 and oleandrin on innate immune functions under viral challenge versus inflammatory culture conditions. Molecules. 2023;16;28(12):4799. doi:10.3390\/molecules28124799"},{"issue":"8","key":"B7","series-title":"PLoS One","first-page":"e0160734","article-title":"Cinobufagin modulates human innate immune responses and triggers antibacterial activity","volume":"11","author":"Xie S","year":"2016","unstructured":"Xie S, Spelmink L, Codemo M, et al. Cinobufagin modulates human innate immune responses and triggers antibacterial activity. PLoS One. 2016;11(8):e0160734. doi:10.1371\/journal.pone.0160734"},{"key":"B8","series-title":"Clin Cosmet Investig Dermatol","first-page":"239","article-title":"Antioxidant, anti-inflammatory, anti-apoptotic, and skin regenerative properties of an Aloe vera-based extract of Nerium oleander leaves (NAE-8\u00ae)","volume":"8","author":"Benson K","year":"2015","unstructured":"Benson K, Newman R, Jensen G. Antioxidant, anti-inflammatory, anti-apoptotic, and skin regenerative properties of an Aloe vera-based extract of Nerium oleander leaves (NAE-8\u00ae). Clin Cosmet Investig Dermatol. 2015;8:239\u2013248 doi:10.2147\/CCID.S79871"},{"issue":"1-2","key":"B9","series-title":"Vet Immunol Immunopathol","first-page":"9","article-title":"Immunological and inflammatory characterization of three canine cell lines: K1, K6 and DH82","volume":"75","author":"Barnes A","year":"2000","unstructured":"Barnes A, Bee A, Bell S, et al. Immunological and inflammatory characterization of three canine cell lines: K1, K6 and DH82. 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Vet Dermatol. 2001;12(6):339\u2013346. doi:10.1046\/j.0959-4493"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/85\/12\/ajvr.24.05.0153.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/85\/12\/ajvr.24.05.0153.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/85\/12\/ajvr.24.05.0153.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T14:09:20Z","timestamp":1733148560000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/85\/12\/ajvr.24.05.0153.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,1]]},"references-count":14,"journal-issue":{"issue":"12"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.24.05.0153","relation":{},"ISSN":["0002-9645","1943-5681"],"issn-type":[{"value":"0002-9645","type":"print"},{"value":"1943-5681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,1]]}}}