{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:05:55Z","timestamp":1786122355098,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Equine herpesvirus type 1 (EHV-1) is a major cause of reproductive loss in mares. This cross-sectional field study evaluated serum concentrations of interleukin-2 (IL-2), interleukin-10 (IL-10), interferon-alpha (IFN-\u03b1), and interferon-gamma (IFN-\u03b3), together with the IL-10\/IL-2 and IFN-\u03b3\/IL-10 ratios, in 26 vaccinated pregnant Thoroughbred mares. The analytical cohort comprised healthy, EHV-1 PCR-negative mares (HM, n = 10), EHV-1 PCR-positive mares sampled within 4 h after fetal expulsion at approximately the sixth month of gestation (AM, n = 9), and EHV-1 PCR-positive pregnant mares without clinically relevant signs (WCS, n = 7). EHV-1 DNA was detected using an EHV-1-specific real-time PCR assay, and serum cytokine concentrations were measured using equine-specific ELISA kits. Serum IFN-\u03b1, IFN-\u03b3, and IL-2 concentrations were significantly higher in both AM and WCS mares than in HM mares (all Holm-adjusted p &lt; 0.001), whereas no statistically significant differences in these cytokines were observed between the AM and WCS groups. IL-10 concentrations were significantly higher in WCS mares than in both HM and AM mares (both adjusted p &lt; 0.01), and HM and AM mares did not differ significantly. The IL-10\/IL-2 ratio was highest in HM mares, intermediate in WCS mares, and lowest in AM mares, with significant differences among all pairwise comparisons (adjusted p \u2264 0.019). Conversely, the IFN-\u03b3\/IL-10 ratio was highest in AM mares, intermediate in WCS mares, and lowest in HM mares, again with significant differences among all pairwise comparisons (adjusted p \u2264 0.044). These findings indicate substantial antiviral immune activation in both EHV-1-positive groups, with a comparatively stronger regulatory immune component in WCS mares and a predominantly pro-inflammatory profile in mares sampled after abortion.<\/jats:p>","DOI":"10.3390\/ani16162455","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T10:12:01Z","timestamp":1786097521000},"page":"2455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Serum Cytokine Profiles in Aborting and Subclinically Infected Pregnant Mares with Equine Herpesvirus Type 1"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2981-2032","authenticated-orcid":false,"given":"\u00d6mer","family":"Deniz","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Veterinary Medicine, Kastamonu University, Kastamonu 37150, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gencay","family":"Ekinci","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Veterinary Medicine, Erciyes University, Kayseri 38280, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"\u00c7itil","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Veterinary Medicine, Erciyes University, Kayseri 38280, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Cesur","family":"Onmaz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Veterinary Medicine, Erciyes University, Kayseri 38280, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3876-2457","authenticated-orcid":false,"given":"Fatih Mehmet","family":"Derelli","sequence":"additional","affiliation":[{"name":"Jockey Club of T\u00fcrkiye, Izmit Central Covering Station, \u0130zmit 41310, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa Cem","family":"Timur","sequence":"additional","affiliation":[{"name":"Jockey Club of T\u00fcrkiye, Equine Health and Veterinary Services, Head Office, Bak\u0131rk\u00f6y, Istanbul 34144, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00f6ksal","family":"Alt\u0131nbay","sequence":"additional","affiliation":[{"name":"Jockey Club of T\u00fcrkiye, Equine Health and Veterinary Services, Head Office, Bak\u0131rk\u00f6y, Istanbul 34144, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alper","family":"Mete","sequence":"additional","affiliation":[{"name":"Jockey Club of T\u00fcrkiye, Istanbul Equine Hospital, Istanbul 34144, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ersin","family":"Ye\u011fen","sequence":"additional","affiliation":[{"name":"Department of Virology, Veterinary Faculty, Istanbul University-Cerrahpasa, Buyukcekmece, Hadimkoy, Istanbul 34555, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5655-8837","authenticated-orcid":false,"given":"Ren\u00e9 van den","family":"Hoven","sequence":"additional","affiliation":[{"name":"Department of Companion Animals and Horses, Equine University Clinic for Internal Medicine and Infectious Diseases, Veterinary University of Vienna, Veterin\u00e4rplatz 1, A-1210 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3198-2580","authenticated-orcid":false,"given":"Francesco","family":"Fazio","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Messina, Via Giovanni Palatucci, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2097-0808","authenticated-orcid":false,"given":"Francesca","family":"Aragona","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Messina, Via Giovanni Palatucci, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Oladunni, F.S., Horohov, D.W., and Chambers, T.M. (2019). EHV-1: A Constant Threat to the Horse Industry. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02668"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Laval, K., Poelaert, K.C.K., Van Cleemput, J., Zhao, J., Vandekerckhove, A.P., Gryspeerdt, A.C., Garr\u00e9, B., van der Meulen, K., Baghi, H.B., and Dubale, H.N. (2021). The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.662686"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Aragona, F., Giannetto, C., Piccione, G., Arfuso, F., Arrigo, F., Costa, A., De Caro, S., Cannuli, A., and Fazio, F. (2025). Effect of Time of Day and Physical Exercise on Inflammatory Biomarkers in Athletic Horses. Front. Vet. Sci., 12.","DOI":"10.3389\/fvets.2025.1608770"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Deniz, \u00d6., Erol, H.S., van den Hoven, R., Onmaz, A.C., Aragona, F., and Fazio, F. (2025). Monitoring Weaning Stress in Fillies and Colts on a Thoroughbred Breeding Farm by Cortisol and Blood Inflammatory Markers: The Benefits of Gradual Separation and Social Support. Animals, 15.","DOI":"10.3390\/ani15243551"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Teer, E., Mukonowenzou, N.C., and Essop, M.F. (2025). The Role of Sustained Type I Interferon Secretion in Chronic HIV Pathogenicity: Implications for Viral Persistence, Immune Activation, and Immunometabolism. Viruses, 17.","DOI":"10.3390\/v17020139"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1093\/infdis\/jiw179","article-title":"Differences in Early Cytokine Production Are Associated with Development of a Greater Number of Symptoms Following West Nile Virus Infection","volume":"214","author":"Hoffman","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetimm.2016.03.009","article-title":"Equine Herpesvirus-1 Infection Disrupts Interferon Regulatory 405 Factor-3 (IRF-3) Signaling Pathways in Equine Endothelial Cells","volume":"173","author":"Sarkar","year":"2016","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mertowska, P., Smolak, K., Mertowski, S., and Grywalska, E. (2023). Immunomodulatory Role of Interferons in Viral and Bacterial Infections. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210115"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Aragona, F., Rizzo, M., Giudice, E., Fazio, F., Costa, A., Di Bella, B., De Caro, S., Arfuso, F., Briglia, M., and Piccione, G. (2025). 391 Circadian Oscillation of Leukocyte Subpopulations and Inflammatory Cytokines over a 24-H Period in Horses. Vet. Sci., 12.","DOI":"10.3390\/vetsci12040386"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"105103","DOI":"10.1016\/j.jevs.2024.105103","article-title":"Monitoring of Inflammatory Blood Biomarkers in Foals with Rhodococcus Equi Pneumonia during Antimicrobial Treatment","volume":"138","author":"Deniz","year":"2024","journal-title":"J. Equine Vet. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Onzere, C.K., Bastos, R.G., Bishop, R.P., Suarez, C.E., and Fry, L.M. (2024). Expression of IL-10 and TGF-\u03921 in Horses Experimentally Infected with T. Equi Merozoites Is Associated with Antibody Production but Not Modulation of pro-Inflammatory Responses. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1370255"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"001987","DOI":"10.1099\/jgv.0.001987","article-title":"Impact of the Host Immune Response on the Development of Equine Herpesvirus Myeloencephalopathy in Horses","volume":"105","author":"Giessler","year":"2024","journal-title":"J. Gen. Virol."},{"key":"ref_13","first-page":"208103","article-title":"Interleukins Affect Equine Endometrial Cell Function: Modulatory Action of Ovarian Steroids","volume":"2014","author":"Hojo","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Satu\u00e9, K., La Fauci, D., Medica, P., Dami\u00e1 G\u00edmenez, E., Cravana, C., and Fazio, E. (2025). Shifts between Pro-Inflammatory and Anti-Inflammatory Profiles in Pregnant Mares: A Review of Physiological Functions. Front. Vet. Sci., 12.","DOI":"10.3389\/fvets.2025.1660759"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Figarska, A., Domino, M., Ma\u015bko, M., and Witkowska-Pi\u0142aszewicz, O. (2023). Serum Cytokine Reactions during Pregnancy in Healthy Mares. Agriculture, 13.","DOI":"10.3390\/agriculture13020331"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1262\/jrd.2012-142","article-title":"Expression of Endometrial Immune-Related Genes Possibly Functioning During Early Pregnancy in the Mare","volume":"59","author":"Tachibana","year":"2013","journal-title":"J. Reprod. Dev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1111\/jvim.16895","article-title":"Vaccination for the Prevention of Equine Herpesvirus-1 Disease in Domesticated Horses: A Systematic Review and Meta-Analysis","volume":"38","author":"Osterrieder","year":"2024","journal-title":"J. Vet. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Aragona, F., Arfuso, F., Fazio, F., De Caro, S., Giudice, E., Monteverde, V., Piccione, G., and Giannetto, C. (2023). Circadian Variation of Peripheral Blood Cells in Horses Maintained in Different Environmental and Management Conditions. Animals, 13.","DOI":"10.3390\/ani13111865"},{"key":"ref_19","unstructured":"World Organisation for Animal Health (WOAH) (2024). Equine Rhinopneumonitis (Infection with Varicellovirus equidalpha1). Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, WOAH. Chapter 3.6.8."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s12985-022-01798-y","article-title":"Development of a Multiplex Droplet Digital PCR Assay for Detection of Enterovirus, Parechovirus, Herpes Simplex Virus 1 and 2 Simultaneously for Diagnosis of Viral CNS Infections","volume":"19","author":"Zhu","year":"2022","journal-title":"Virol. J."},{"key":"ref_21","unstructured":"Quinn, P.J., Markey, B.K., Leonard, F.C., FitzPatrick, E.S., Fanning, S., and Hartigan, P.J. (2011). Veterinary Microbiology and Microbial Disease, Wiley-Blackwell. [2nd ed.]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.cyto.2016.09.018","article-title":"Multiplex Assay Reliability and Long-Term Intra-Individual Variation of Serologic Inflammatory Biomarkers","volume":"90","author":"McKay","year":"2017","journal-title":"Cytokine"},{"key":"ref_23","unstructured":"World Organisation for Animal Health (OIE) (2017). Equine Rhinopneumonitis (Infection with Equid Herpesvirus-1 and -4). Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, OIE. Chapter 2.5.9."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"593","DOI":"10.2746\/042516408X333399","article-title":"Experimental reactivation of equine herpesvirus-3 following corticosteroid treatment","volume":"40","author":"Barrandeguy","year":"2008","journal-title":"Equine Vet. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.diagmicrobio.2009.03.014","article-title":"Detection of pathogenic Leptospira spp. through TaqMan polymerase chain reaction targeting the LipL32 gene","volume":"64","author":"Stoddard","year":"2009","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_26","first-page":"004-2026","article-title":"Molecular Prevalence of Equine Herpesvirus Type 1 and Equine Herpesvirus Type 4 in Thoroughbred and Arabian Horse Facilities in T\u00fcrkiye","volume":"1","author":"Mete","year":"2026","journal-title":"Acta Vet. Hung."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/j.1939-1676.2009.0304.x","article-title":"Equine Herpesvirus-1 Consensus Statement","volume":"23","author":"Lunn","year":"2009","journal-title":"J. Vet. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.2460\/ajvr.69.12.1595","article-title":"Risk Factors for Development of Neurologic Disease after Experimental Exposure to Equine Herpesvirus-1 in Horses","volume":"69","author":"Allen","year":"2008","journal-title":"Am. J. Vet. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6564","DOI":"10.1016\/j.vaccine.2012.08.046","article-title":"Strain Impact on Equine Herpesvirus Type 1 (EHV-1) Abortion Models: Viral Loads in Fetal and Placental Tissues and Foals","volume":"30","author":"Gardiner","year":"2012","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lee, A.J., and Ashkar, A.A. (2018). The Dual Nature of Type I and Type II Interferons. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02061"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e0109224","DOI":"10.1128\/spectrum.01092-24","article-title":"Immune Horses Rapidly Increase Antileukoproteinase and Lack Type I Interferon Secretion during Mucosal Innate Immune Responses against Equine Herpesvirus Type 1","volume":"12","author":"Holmes","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.4049\/jimmunol.130.4.1784","article-title":"Interleukin 2-Mediated Immune Interferon (IFN-Gamma) Production by Human T Cells and T Cell Subsets","volume":"130","author":"Kasahara","year":"1983","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.vetimm.2011.06.032","article-title":"Infection of Peripheral Blood Mononuclear Cells with Neuropathogenic Equine Herpesvirus Type-1 Strain Ab4 Reveals Intact Interferon-\u03b1 Induction and Induces Suppression of Anti-Inflammatory Interleukin-10 Responses in Comparison to Other Viral Strains","volume":"143","author":"Wagner","year":"2011","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Khan, M.Z., Ji, Y., Fan, X., Liu, Y., Liu, W., and Wang, C. (2025). Equine Herpesvirus Infections: Treatment Progress and Challenges in Horses and Donkeys. Vet. Sci., 12.","DOI":"10.3390\/vetsci12111082"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6104054","DOI":"10.1155\/2017\/6104054","article-title":"IL-10: A Multifunctional Cytokine in Viral Infections","volume":"2017","author":"Rojas","year":"2017","journal-title":"J. Immunol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Guo, Z., He, Q., Zhang, Y., Li, Y., and Zhang, Z. (2025). Mechanisms of Interleukin-10-Mediated Immunosuppression in Viral Infections. Pathogens, 14.","DOI":"10.3390\/pathogens14100989"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/nm1492","article-title":"Interleukin-10 Determines Viral Clearance or Persistence in Vivo","volume":"12","author":"Brooks","year":"2006","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/glia.20045","article-title":"Interleukin-10 Attenuates Production of HSV-Induced Inflammatory Mediators by Human Microglia","volume":"47","author":"Marques","year":"2004","journal-title":"Glia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.vetmic.2014.01.018","article-title":"Innate Immune Responses of Airway Epithelial Cells to Infection with Equine Herpesvirus-1","volume":"170","author":"Ashton","year":"2014","journal-title":"Vet. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nri.2017.64","article-title":"The Unique Immunological and Microbial Aspects of Pregnancy","volume":"17","author":"Mor","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1600-0897.2010.00852.x","article-title":"Th1\/Th2\/Th17 and Regulatory T-Cell Paradigm in Pregnancy","volume":"63","author":"Saito","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"104453","DOI":"10.1016\/j.jri.2025.104453","article-title":"Assessing the Impact and Risk of Immunomodulatory Compounds on Pregnancy","volume":"169","author":"Maier","year":"2025","journal-title":"J. Reprod. Immunol."},{"key":"ref_43","first-page":"16","article-title":"Molecular Prevalence of Equine Alphaherpesvirus-1 Shedding in Healthy Broodmares in Ontario","volume":"90","author":"Cooper","year":"2026","journal-title":"Can. J. Vet. Res."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/16\/2455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T10:19:53Z","timestamp":1786097993000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/16\/2455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":43,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ani16162455"],"URL":"https:\/\/doi.org\/10.3390\/ani16162455","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]}}}