The effects of feeding mixed tocopherol oil on whole blood neutrophil chemiluminescent burst and immunometabolic-related gene expression in lactating dairy cows

Authors: QU, Y - US Department Of Agriculture (USDA); Elsasser, Theodore; Kahl, Stanislaw; GARCIA, M - University Of Maryland; SCHOLTE, C - University Of Maryland; Connor, Erin; SCHROEDER, G - Cargill, Incorporated; MOYES, K - University Of Maryland

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/11/2018
Publication Date: 5/1/2018
Citation: Qu, Y., Elsasser, T.H., Kahl, S., Garcia, M., Scholte, C., Connor, E.E., Schroeder, G., Moyes, K. 2018. The effects of feeding mixed tocopherol oil on whole blood neutrophil chemiluminescent burst and immunometabolic-related gene expression in lactating dairy cows. Journal of Dairy Science. 101(5):4332-4342. https://doi.org/10.3168/jds.2017-13902.
DOI: https://doi.org/10.3168/jds.2017-13902

Interpretive Summary: Animals are continually challenged in their environment by microorganisms that can cause disease. Although antibiotic therapy is often thought of as a first line of defense against the invading organisms and return to a state of health, the actual first responders are blood cells of the immune system called neutrophils. Through a complex signaling system, detection of infective organisms mobilized neutrophils to migrate in the body to the site of infection and destroy the disease-causing microorganisms. In doing so these immune cells "capture" the microbes and destroy them with an intense release of oxidizing compounds within the cell. At the present time, there is a major thrust underway to curb the overuse of antibiotic drugs in food animals and as a recourse develop strategies that can assist the animal in maintaining its health before the invasion of the animal be a microbe can cause active disease. Researchers at the USDA in Beltsville and University of Maryland, College Park, added a complex mixture of various vitamin E components called mixed tocopherols (Tmix) and fed it to dairy cows to test the impact of such feeding on the biological function of the neutrophiles. Feeding Tmix for as short a time as one week was in no way harmful to the function of the neutrophils; they maintained their robust production of intracellular oxidizing compounds as stimulated by natural and chemical signals. Feeding Tmix did improve the release of molecules from the neutrophils that are key to further signaling the immune system to challenge invading disease-causing microbes. The data suggest that short-term feeding Tmix may be a functionally efficient means of boosting immune function in food animals in anticipation of potential exposure of the animals to various stresses that could increase the chance of infecting organisms to gain a foothold and cause disease.

Technical Abstract: Due to some basic chemical structure differences, the four major tocopherol isoforms differ in their biochemical reactivity and cellular effects. Alpha-tocopherol has been well-studied regarding effects on bovine PMN function and its involvement in respiratory burst. However, no studies have identified the effect of supplementing a mixed tocopherol oil (Tmix) particularly enriched in non-a-tocopherol isoforms (i.e., y- and d-isoforms) on fundamental immunometabolic changes in dairy cows. Therefore, the objective of this study was to investigate how short-term feeding of vegetable oil-derived mixed tocopherol supplement (with high levels of y- and d-isoforms) alters specific biomarkers of metabolism, whole blood hematology and respiratory burst, and PMN immunometabolic-related gene expression. Healthy multiparous Holstein cows (n=12; DIM: 179 ± 17 d) were fed Tmix (620 g/d) for 7 consecutive days. Jugular blood (EDTA anticoagulant) was collected from all cows on d 0 prior to feeding and on d 7 post to Tmix feeding. Total stimulated respiratory burst activity (RBA) was assessed in whole blood, tocopherol isoform concentrations, metabolites, and hormones were measured in plasma. For gene expression analysis, isolated PMN cells were incubated with LPS at a final concentration of either 0.0 or 1.5 µg/mL. Data were analyzed as a complete randomized design. Tmix increased the concentration of a- and y-tocopherol after feeding (P < 0.01). Tmix did not alter plasma metabolites (P > 0.05) and hormones (P > 0.05), except tended to decrease non-esterified fatty acids (P = 0.09). Tmix did not alter the whole blood RBA (P = 0.90) and hematology (P > 0.05) except increased monocytes (P = 0.04). For gene expression analysis, LPS challenge increased the expression of pro-inflammatory genes TNFA and IL6 (P < 0.05). However, Tmix did not alter the patterns of LPS-affected expression of genes associated with the immune or metabolic response. In conclusion, short-term feeding of Tmix did not impair whole blood RBA, hematology or alter the immunometabolic response of genes to LPS challenge in bovine blood PMN. The data are consistent with the concept that supplementing Tmix does increase plasma levels of the a- and y- tocopherol but does not interfere with normal immune or metabolic function as assessed with the general physiological biomarkers studied here.