{
  "abstract": "Background: 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, β-caryophyllene (BCP), could affect immune function in heat-stressed dairy cows.\n\nMethods: 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 × 2 factorial design ( n = 10 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\nResults: 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.\n\nConclusions: 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ruminant Science, Institute of Animal Sciences, Agricultural Research Organization, Volcani Institute , ,",
    "Department of Animal Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem , ,",
    "Intra-Institutional Services Unit, Volcani Institute , ,",
    "Department of Animal Science, Michigan State University , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Liam Hubner"
    },
    {
      "affs": [
        0
      ],
      "name": "Priscila dos S. Silva"
    },
    {
      "affs": [
        0
      ],
      "name": "Yana Butenko"
    },
    {
      "affs": [
        0
      ],
      "name": "Ben Shattenstein"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuri Portnick"
    },
    {
      "affs": [
        1
      ],
      "name": "Tali Dogot"
    },
    {
      "affs": [
        1
      ],
      "name": "Lir Marcus"
    },
    {
      "affs": [
        2
      ],
      "name": "Ahmed Nasser"
    },
    {
      "affs": [
        2
      ],
      "name": "Mohamed Samara"
    },
    {
      "affs": [
        3
      ],
      "name": "Barry J. Bradford"
    },
    {
      "affs": [
        0
      ],
      "name": "Maya Zachut"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f9sgr66s3wdy1.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1931588",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661458/?tool=EBI",
  "id": "f9sgr66s3wdy1",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13661458",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1103|Effects of Environmental Stressors on Livestock"
    ]
  ],
  "openalex": "W7214931366",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661458/pdf/?tool=EBI",
  "pmcid": "PMC13661458",
  "pmid": null,
  "published": "2026-09-30",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/f9sgr66s3wdy1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:20Z",
      "native_id": "PMC:PMC13661458",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13661458"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1931588",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1931588/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1103|Effects of Environmental Stressors on Livestock",
      "subfield": "zoology-behaviour"
    }
  ],
  "title": "Immune-modulating effects of dietary cannabinoid-receptor 2 agonist beta-caryophyllene and cooling frequency in dairy cows under environmental heat load",
  "title_text": "Immune-modulating effects of dietary cannabinoid-receptor 2 agonist beta-caryophyllene and cooling frequency in dairy cows under environmental heat load",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:15Z",
  "url": "https://research.draconitic.com/paper/f9sgr66s3wdy1",
  "venue": "Frontiers in immunology",
  "versions": []
}