{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:55:07Z","timestamp":1790747707873,"version":"4.1.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001269","name":"BARD","doi-asserted-by":"publisher","award":["IS-5640-24D"],"award-info":[{"award-number":["IS-5640-24D"]}],"id":[{"id":"10.13039\/501100001269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Environmental heat load negatively affects productivity, welfare and immune function in livestock. The endocannabinoid system regulates immune function, and activation of the cannabinoid receptor 2 (CB2) has mostly anti-inflammatory effects. We hypothesized that increased cooling frequency and providing a dietary CB2 agonist, \u03b2-caryophyllene (BCP), could affect immune function in heat-stressed dairy cows.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty mid-lactation Holstein dairy cows exposed to environmental heat load conditions were assigned randomly according to their milk production, body weight, lactation number and days in lactation to one of 4 treatments: Either controls (CTL) or supplemented with BCP (at 5 mg\/kg BW), and half of the cows from each dietary treatment were cooled with either 3 or 6 cooling sessions (CS) a day, creating a 2 \u00d7 2 factorial design (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010 in each group): CTL-6CS, CTL-3CS, BCP-6CS, and BCP-3CS. Milk production, feed intake and behavior parameters were measured. At week 5, six cows from each group were challenged with intra-mammary lipopolysaccharide (LPS). Vaginal temperatures and blood samples were taken for stress and immune function parameters. Data were analyzed for main effects of BCP, CS, time and their interactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BCP supplementation increased plasma BCP concentrations vs. CTL. Before the LPS-challenge, production and feed intake were not affected by BCP, but BCP increased the duration of resting bouts and reduced eating time. 6CS-cows had longer rumination time and lower panting time and respiratory rate compared to 3CS. During the LPS-challenge, BCP-cows exhibited lower vaginal temperatures during peak fever, with lowest temperatures in BCP-6CS cows. Plasma cortisol area under the curve (AUC) tended to be lower in BCP-6CS than in CTL-3CS. BCP-cows had lower blood monocyte percentages post-LPS compared to CTL; while mean platelet volume, mass and mass-distribution-width were increased in BCP vs. CTL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dietary BCP during heat load lowered peak fever response to inflammatory-challenge and had moderate and specific immune-modulating and stress-mitigating effects, with some added effects with increased CS frequency. Thus, dietary supplementation with a CB2 agonist can be a novel strategy to improve immune function, stress response and welfare of dairy cows.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1931588","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:56:44Z","timestamp":1790744204000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune-modulating effects of dietary cannabinoid-receptor 2 agonist beta-caryophyllene and cooling frequency in dairy cows under environmental heat load"],"prefix":"10.3389","volume":"17","author":[{"given":"Liam","family":"Hubner","sequence":"first","affiliation":[{"name":"Department of Ruminant Science, Institute of Animal Sciences, Agricultural Research Organization, Volcani Institute","place":["Rishon LeZion, Israel"]},{"name":"Department of Animal Science, The Robert H. 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