Temporal bias in physiological and immune responses to endotoxin challenge in bovine calves

Globally, livestock serves as an important source of food and nutritional security, thus warrants robust animal care and management. Evidence suggests that there exists a relationship between circadian rhythm and immune-endocrine response to a homeostatic challenge. In the present investigation, fifteen prepubertal bovine calves of 6-8 months age were randomly distributed into three groups; Morning, Afternoon, and Evening groups with five calves in each group. Four calves from each group were intravenously challenged with endotoxin (E. coli 055:B5 @ 0.5 μg/kg bw). The Morning group was challenged at 6 o'clock (6 AM), Afternoon group at 14 o'clock (2 PM), and Evening group at 22 o'clock (10 PM) in a 24-h circadian cycle. One calf from every group received 10 ml normal saline intravenously to serve as placebo. The responses for basic physiological parameters viz; rectal temperature, respiration rate and heart rate were recorded before injection and at an interval of 1, 2, 4, 8, and 12 h after the endotoxin challenge. Blood (7 ml) from each animal was drawn aseptically from the jugular vein in heparinized vacutainers before challenge and at an interval of 1, 2, 4, 8 and 12 h after the challenge. Rectal temperature, heart rate, and respiration rate recorded as area under curve (AUC) after antigenic challenge were significantly (p < 0.001) different amongst the groups with highest values in the Morning group. Similarly, the responses to endotoxin insult for total leukocyte count (TLC) and blood glucose recorded a significant (p < 0.05) dip from the base values after the challenge. The responses of immune markers like IL-1β, IL-6, IL-10, and TNF-α to the challenge were significantly (p < 0.05) elevated from base values which peaked by 2-4 h post-challenge in all the groups and receded to the baseline levels by 12 h after the challenge. The change in IL-1β recoded as AUC was lowest in the Evening group, whereas, IL-6, IL-10, and TNF-α were lowest in the Morning group. The present study confirms that bovines respond differentially to the endotoxin challenge over a 24-h circadian cycle that may ultimately influence the immune response, disease progression and therapeutic regimes. Further research in this area should open a new window of chronotherapy in veterinary medicine.