{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:47:14Z","timestamp":1790387234930,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,6,4]],"date-time":"2019-06-04T00:00:00Z","timestamp":1559606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Progestins are immunomodulatory in a variety of species. In the horse, the most commonly administered synthetic progestin is altrenogest (ALT), but its effect on the immune system of the non\u2010pregnant mare is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood mononuclear cells (PBMCs) from diestrous mares were incubated with varying concentrations of progesterone (P4) or ALT to assess intracellular production of IFN\u03b3 and the expression of select cytokines. Additionally, ten mares received either ALT or VEH daily utilizing a switchback design beginning on the day of ovulation and continuing for 7\u00a0days. Circulating PBMCs and endometrial biopsies were obtained to assess the production and expression of the same cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro, both P4 and ALT caused a dose\u2010dependent decrease in intracellular IFN\u03b3 in PBMCs. P4 caused a dose\u2010dependent decrease in the expression of<jats:italic>IFN\u03b3, IL\u201010<\/jats:italic>and<jats:italic>IL\u20104,<\/jats:italic>while ALT caused an increase in the expression of<jats:italic>IL\u20106<\/jats:italic>and<jats:italic>IL\u20101\u03b2<\/jats:italic>in PBMCs. In vivo, ALT suppressed the intracellular levels of IFN\u03b3 in PBMCs on d6. While control mares experienced a decrease in<jats:italic>IL\u20101\u03b2<\/jats:italic>expression from d0 to d6, ALT\u2010treated mares did not. In the endometrium, ALT increased the expression of<jats:italic>IL\u20101RN<\/jats:italic>and<jats:italic>IFN\u03b3<\/jats:italic>in comparison with VEH\u2010treated mares.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>P4 and ALT appear to alter the immune system of the non\u2010pregnant mare both systemically in addition to locally within the endometrium. Further research is necessary to determine the pathways through which this synthetic progestin functions on the immune system of the horse, and the consequences it may have.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13145","type":"journal-article","created":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T02:13:46Z","timestamp":1557800026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Alteration of the mare's immune system by the synthetic progestin, altrenogest"],"prefix":"10.1111","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0518-4809","authenticated-orcid":false,"given":"Carleigh Elizabeth","family":"Fedorka","sequence":"first","affiliation":[{"name":"Department of Veterinary Science University of Kentucky Lexington Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0502-0276","authenticated-orcid":false,"given":"Barry 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