Elucidating natural variations in the proinflammatory response of the domesticated bovine using an endotoxemia model

Authors: Carroll, Jeffery - Jeff Carroll; Sanchez, Nicole; Broadway, Paul; WELSH, THOMAS - Texas A&M Agrilife; RANDEL, RONALD - Texas A&M Agrilife

Submitted to: Frontiers in Immunology
Publication Type: Abstract Only
Publication Acceptance Date: 2/7/2018
Publication Date: 8/31/2018
Citation: Carroll, J.A., Sanchez, N.C., Broadway, P.R., Welsh, T.H., Randel, R.D. 2018. Elucidating natural variations in the proinflammatory response of the domesticated bovine using an endotoxemia model. Joint XII Congress of the Latin American Association of Immunology and XXIII Congress of the Mexican Society of Immunology meeting, May 14-18, 2018. Frontiers ISBN: 978-2-88945-511-9; doi:10.3389/978-2-88945-511-9; Pp. 155-157.
DOI: https://doi.org/10.3389/978-2-88945-511-9

Interpretive Summary:

Technical Abstract: The innate immune system is an evolutionarily ancient and highly conserved mechanism designed to fight disease within the body. It represents the antigen-nonspecific defense mechanisms of the immune system that are elicited immediately or within several hours (0 to 4 hours) after exposure to an antigen. Beyond the physical barriers such as skin, mucosal secretions, tears, urine, stomach acid and cilia, the innate immune system serves as the first line of defense for providing immunological protection. When functioning properly, the innate immune system eliminates the majority of pathogenic organisms that elude the body’s physical barriers and enter into the animal. While the term “innate immunity” implies that this component of the immune system is stable or resolute, this is not always true. In fact, while the innate immune system is always present to some degree, it can be either enhanced or compromised due to numerous factors such as wounds, dehydration, nutritional restriction, genetic predispositions, exposure to stress, and/or natural variations that exist within a population. Through a series of research experiments, we have documented the existence of naturally occurring variations in the proinflammatory response of the innate immune system in cattle following an i.v. challenge with a bolus dosage of endotoxin. Specifically, we have demonstrated differences in the proinflammatory response due to gender and animal flightiness. In a study that evaluated the proinflammatory response in prepubertal Bos indicus calves, six healthy pure-bred Brahman heifers and five healthy purebred Brahman bulls (average age = 253 ± 19.9 and 288 ± 47.9 days; average body weight = 194 ± 11 kg and 247 ± 19 kg for heifers and bulls, respectively) were challenged i.v. with an Escherichia coli-derived lipopolysaccharide (LPS ) at a dose of 0.25 ug/kg body weight at 0 h. Blood samples for serum were collected at 30-min intervals and whole blood samples were collected at 1-h intervals from -2 to 8 h, and at 12 h and 24 h relative to the LPS challenge. One trained observer assessed and recorded each animal’s sickness behavior score by visual observation immediately prior to each blood collection. Calves were also fitted with rectal temperature (RT) monitoring devices that recorded RT at 1-min intervals throughout the duration of the study. Results from this study revealed some significant biological differences in the proinflammatory response between heifers and bulls. Specifically, heifers maintained greater RT (P < 0.01) and serum concentrations of tumor necrosis factor-alpha (TNF; P < 0.01) compared to bulls. However, sickness scores (P < 0.01) and serum concentrations of interferon-gamma (IFN; P < 0.03) were greater in bulls than in heifers. Serum concentrations of cortisol and interleukin-1 beta (IL-1) were not different (P > 0.10) between heifers and bulls. Additionally, circulating lymphocytes and neutrophils were not different (P < 0.10) between heifers and bulls post-LPS challenge. Given that the calves used in this study were prepubertal, we speculate that the differences observed in the proinflammatory response are independent of sex hormones, and most likely reflect conserved sexually dimorphic proinflammatory responses. To determine the potential impact of animal flightiness (i.e., temperament) on the proinflammatory response of cattle, 24 purebred Brahman yearling bulls (10 mo of age) were selected based on temperament score which is calculated by taking the average of the exit velocity (EV; flight speed) and pen score (PS) for each animal. Bulls were ranked into 3 groups: Calm, lowest temperament score (n=8; 0.87 m/s EV and 1 PS), Intermediate (n=8; 1.59 m/s EV and 2.25 PS), and Temperamental, highest temperament score (n=8; 3.70 m/s EV and 4.88 PS). Bulls were fitted with indwelling jugular catheters and RT devices that recorded RT