Immunomodulation by cannabidiol in bovine primary ruminal epithelial cells

Authors: KENT-DENNISON, CORAL - ORISE FELLOW; Klotz, James

Submitted to: BMC Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/27/2023
Publication Date: N/A
Citation: N/A

Interpretive Summary: There is increasing interest in the use of industrial hemp waste biomass as a possible feedstuff for ruminants. There are numerous bioactive compounds in hemp, but one of particular interest is cannabidiol or CBD. This compound may be in relatively low concentrations in processed hemp biomass, but there is evidence that even low levels could elicit bioactive effects. There is a growing amount of evidence that suggests that CBD may be useful in modulating inflammatory responses. There is interest in how CBD could be used as an anti-inflammatory treatment in the gut of cattle. This study evaluated effects of CBD to mitigate the effects of an induced inflammatory response in rumen epithelial cells isolated from the foregut of cattle. Through the evaluation of genes associated with inflammatory pathways, this study found that inclusion of CBD does influence the inflammatory response of rumen epithelial cells. Further, CBD can be used as a treatment for ongoing inflammation or as a preventative treatment to minimize the onset and negative consequences of inflammation in the gut. These results are relevant to operations where gut inflammation can be an ongoing concern, such as feedlots and high production dairies. This work will also be of interest to researchers that are interested in cannabinoids as natural products in animal feed as well as creating a value-added product out of spent hemp biomass.

Technical Abstract: Ruminant livestock experience a number of challenges, including high concentrate diets, weaning and transport, which can increase their risk of disorders such as ruminal acidosis, and the associated inflammation of the ruminal epithelium. Cannabidiol (CBD), a phytochemical from hemp (Cannabis sativa), is a promising target as a therapy for gastrointestinal inflammation, and may be extremely valuable as either a treatment or prophylactic. However, the effects of CBD in the the ruminant gastrointestinal tract have not been explored, in part due to the restrictions on feeding hemp to livestock. Therefore, the objective of this study was to investigate the immunomodulatory properties of CBD using a model of inflammation in primary ruminal epithelial cells (REC). In addition, CBD dose was evaluated for possible cytotoxic effects. Negative effects on cell viability were not observed when REC were exposed to 10 µM CBD. However, when the dose was increased to 50 µM for 24 h, there was a significant cytotoxic effect. When 10 µM CBD was added to culture media as treatment for inflammation induced with lipopolysaccharide (LPS), expression of genes encoding for pro-inflammatory cytokine IL1B was less compared to LPS exposure alone, and CBD resulted in a down-regulation of IL6. As a pre-treatment, prior to LPS exposure, REC had decreased expression of IL6 and CXCL10 while CBD was present in the media, but not when it was removed prior to addition of LPS. Results suggest that CBD may reduce cytokine transcription both during LPS-induced inflammation and when used preventatively, although these effects were dependent on its continued presence in the culture media. Overall, these experiments provide evidence of an immunomodulatory effect by CBD during a pro-inflammatory response in primary REC in culture.