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The systemic inflammatory response to intramuscular endotoxin challenge in dairy heifers.

T. M. Sullivan



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The systemic inflammatory response to intramuscular endotoxin challenge in dairy heifers.
T. M. Sullivan*1,3, A. Sharma1,3, K. Lamers1,3, A. Canovas1,3, B. Mallard2,3, N. A. Karrow1,3. 1Ontario Agricultural College, Department of Animal Biosciences Guelph, ON, Canada, 2Ontario Veterinary College, Department of Pathobiology Guelph, ON, Canada, 3University of Guelph Guelph, ON, Canada.

Dairy cattle routinely face a variety of stressors. Specifically, climate change has resulted in more frequent heat stress events that increase the incidence of bacterial infections by inducing conditions like leaky gut syndrome, whereby the integrity of the intestinal epithelium is compromised allowing for luminal bacteria and bacterial lipopolysaccharide (LPS) to infiltrate the host's bloodstream resulting in systemic stimulation of the innate immune system. LPS is a well characterized and biologically relevant microbe-associated molecular pattern that makes up the outer membrane of gram-negative bacteria and is known to contribute to inflammatory disorders including mastitis, acidosis and septicemia. In the present study, Holstein calves (n = 72) were intramuscularly challenged with 0 (saline), 100, 200 or 400 ng/kg of LPS, and serum was collected hourly for 8 h to profile changes in circulatory stress biomarkers. All LPS treatment groups demonstrated distinct cortisol responses at 2 h post-LPS challenge (P < 0.05). Additionally, animals challenged with 200 ng/kg (P < 0.01) and 400 ng/kg (P < 0.001) of LPS demonstrated significant changes in serum cortisol concentrations for up to 4 h. A total of 8 cytokines, including TNFα, IL-10 and IL-6, were found to be dose-dependently induced between 2 and 4 h. The expression of immune-related miR-29b (P < 0.1), miR-31 (P < 0.05), miR-223 (P < 0.05), miR-1246 (P < 0.001) were also increased significantly over time. The dairy cattle stress response is a dynamic process, and the present study suggests that there is a peak window of time when cortisol, miRNA and cytokines are induced to regulate the inflammatory response. Variability in the inflammatory response warrants further investigation to better understand the contribution of genetics and associations between immune health and the stress response.

Keywords: sustainability, stress, resilience.