Frontiers in immunology · 2026
Immune-modulating effects of dietary cannabinoid-receptor 2 agonist beta-caryophyllene and cooling frequency in dairy cows under environmental heat load.
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Hubner Liam, Silva Priscila Dos S, Butenko Yana, Shattenstein Ben, Portnick Yuri, Dogot Tali, Marcus Lir, Nasser Ahmed, Samara Mohamed, Bradford Barry J, Zachut Maya
Аннотация
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.
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.