{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:46:16Z","timestamp":1785732376702,"version":"3.56.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Pigs are attracting increasing attention as a large-animal model with translational relevance in biomedical research. They share several immunological similarities with humans, although the pig immune system has not been fully characterized yet, also at the level of macrophage polarization. A better understanding of porcine macrophage polarization could improve translational studies, allowing a better interpretation of\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    results. In this study, we performed a detailed characterization of the impact of two poorly studied cytokines [interleukin-1\u03b2 (IL-1\u03b2) and its receptor antagonist IL-1Ra] on porcine monocyte-derived macrophage (moM\u0424) phenotype and functions. The effects of these IL-1 family members were investigated through microscopy, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and gene expression studies. We observed that stimulation with IL-1\u03b2 increased CD14, SLA-I, and SLA-II DR expression, and enhanced the release of pro-inflammatory cytokines, particularly IL-6, IL-12, and IL-1\u03b1 at higher concentrations, and the expression of several antiviral and pro-inflammatory genes, including\n                    <jats:italic>JUN<\/jats:italic>\n                    ,\n                    <jats:italic>FOS<\/jats:italic>\n                    , and\n                    <jats:italic>MAP3K1<\/jats:italic>\n                    . The concomitant release of IL-10 and IL-1Ra suggests that IL-1\u03b2 stimulation may also activate compensatory regulatory feedback mechanisms aimed at limiting excessive inflammation. In contrast, IL-1Ra had limited effects on surface marker expression but increased IL-10 release. A small but significant release of IL-1\u03b1 was also observed, as well as a trend toward enhanced\n                    <jats:italic>IL1B<\/jats:italic>\n                    expression at 24\u00a0h, suggesting a potential regulatory interaction within the IL-1 axis. MoM\u0424 stimulated with IL-1Ra was also able to release high levels of IL-12 in response to stimulation with a TLR-3 ligand [polyinosinic\u2013polycytidylic acid (poly I:C)], with an intensity comparable to moM\u0424 and moM\u0424 stimulated with IL-1\u03b2. Our data suggest that porcine macrophages attempt to maintain a balance between IL-1\u03b2 and IL-1Ra, as a defense mechanism to control inflammation, by counteracting each other\u2019s activity. Overall, in this work, we provided a better understanding of porcine macrophage polarization, which could benefit translational studies using this large-animal model.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1869718","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:27:48Z","timestamp":1785731268000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic and functional changes to porcine monocyte-derived macrophages triggered by IL-1\u03b2 and its receptor antagonist IL-1Ra"],"prefix":"10.3389","volume":"17","author":[{"given":"Emanuela","family":"Giaconi","sequence":"first","affiliation":[{"name":"Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna","place":["Sassari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samanta","family":"Mecocci","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Perugia","place":["Perugia, Italy"]},{"name":"Department of Innovation in Biological, Agro-Food and Forest System (DIFAB), University of Tuscia","place":["Viterbo, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Zinellu","sequence":"additional","affiliation":[{"name":"Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna","place":["Sassari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Margarita","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, University of Sassari","place":["Sassari, SS, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Morrone","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Sassari","place":["Sassari, SS, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Columbano","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Sassari","place":["Sassari, SS, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Bogliolo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Sassari","place":["Sassari, SS, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Barroso-Ar\u00e9valo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Animal Surgery, Faculty of Veterinary Medicine, Complutense University of Madrid","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Cappelli","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Franzoni","sequence":"additional","affiliation":[{"name":"Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna","place":["Sassari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s40828-022-00163-4","article-title":"Macrophages: shapes and functions","volume":"8","author":"Lendeckel","year":"2002","journal-title":"Chem Texts"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1733","article-title":"Monocyte and macrophage heterogeneity","volume":"5","author":"Gordon","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00370","article-title":"The many alternative faces of macrophage 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