Immune-modulating effects of dietary cannabinoid-receptor 2 agonist beta-caryophyllene and cooling frequency in dairy cows under environmental heat load
4 affiliations
- 1Department of Ruminant Science, Institute of Animal Sciences, Agricultural Research Organization, Volcani Institute , ,
- 2Department of Animal Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem , ,
- 3Intra-Institutional Services Unit, Volcani Institute , ,
- 4Department of Animal Science, Michigan State University , , ,
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.
Methods: 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.
Results: 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.
Conclusions: 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.
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BibTeX
@article{hubner2026immunemodulating,
title = {{Immune-modulating effects of dietary cannabinoid-receptor 2 agonist beta-caryophyllene and cooling frequency in dairy cows under environmental heat load}},
author = {Liam Hubner and Priscila dos S. Silva and Yana Butenko and Ben Shattenstein and Yuri Portnick and Tali Dogot and Lir Marcus and Ahmed Nasser and Mohamed Samara and Barry J. Bradford and Maya Zachut},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1931588},
url = {https://europepmc.org/article/PMC/PMC13661458},
note = {CC BY},
}
RIS
TY - JOUR
TI - Immune-modulating effects of dietary cannabinoid-receptor 2 agonist beta-caryophyllene and cooling frequency in dairy cows under environmental heat load
AU - Liam Hubner
AU - Priscila dos S. Silva
AU - Yana Butenko
AU - Ben Shattenstein
AU - Yuri Portnick
AU - Tali Dogot
AU - Lir Marcus
AU - Ahmed Nasser
AU - Mohamed Samara
AU - Barry J. Bradford
AU - Maya Zachut
PY - 2026
DA - 2026/09/30
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1931588
UR - https://europepmc.org/article/PMC/PMC13661458
AB - 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. Methods: 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. Results: 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. Conclusions: 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.
SN - 1664-3224
ER -