Prenatal immune stimulation alters the postnatal acute phase and metabolic responses to an endotoxin challenge in weaned beef heifers

Authors: Carroll, Jeffery - Jeff Carroll; Sanchez, Nicole; Broadway, Paul; SILVA, GLEISE - University Of Florida; RANCHES, JULIANA - University Of Florida; WARREN, JULIE - University Of Florida; ARTHINGTON, JOHN - University Of Florida; LANCASTER, PHILLIP - Kansas State University; MORIEL, PHILIPE - University Of Florida

Submitted to: Translational Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/24/2021
Publication Date: 7/7/2021
Citation: Carroll, J.A., Sanchez, N.C., Broadway, P.R., Silva, G.M., Ranches, J., Warren, J., Arthington, J.D., Lancaster, P.A., Moriel, P. 2021. Prenatal immune stimulation alters the postnatal acute phase and metabolic responses to an endotoxin challenge in weaned beef heifers. Translational Animal Science. 5(3). https://doi.org/10.1093/tas/txab097.
DOI: https://doi.org/10.1093/tas/txab097

Interpretive Summary: Our group has previously shown that a mild immune challenge during late pregnancy can change early life immune function in beef calves. By exposing fetal calves to a mild immune challenge, we hoped to better prepare them to deal with diseases later in life. Data from this prior study showed that a single low-dose of endotoxin to pregnant cows in late pregnancy altered the immune response, metabolic response, and performance of weaned calves. Therefore, our group sought to determine if giving this same endotoxin during all three trimesters would cause even greater changes. The results show that immune and metabolic responses in calves were in fact altered by fetal exposure to endotoxin during all three trimesters. These results also support previous research. This research demonstrates an ability to re-program the immune system of cattle in a way that may increase disease resilience. This information will be of interest to beef cattle producers and scientists working in the field of beef cattle health and management.

Technical Abstract: This study evaluated whether administration of lipopolysaccharide (LPS) at each trimester during gestation would alter the acute phase (APR) and metabolic responses to a postnatal LPS challenge in weaned heifers. Pregnant crossbred multiparous cows (n = 50) were randomized into prenatal immune stimulation (PIS; n = 24; administered 0.1 µg/kg BW LPS subcutaneously at 71 ± 2, 170 ± 2 and 234 ± 2 d of gestation) and saline (CON; n = 26) groups. From these treatment groups, heifer calves (n = 12 PIS and 11 CON) were identified at weaning (244 ± 3 d of age) to subsequently receive an LPS challenge. On d 0, heifers were fitted with indwelling vaginal temperature (VT) devices, jugular catheters, and moved into individual stalls. On d 1, heifers were challenged i.v. with LPS (0.5 µg/kg BW) at 0 h. Blood samples were collected and sickness behavior scores (SBS) were recorded at 0.5h intervals from -2 to 8 h and at 24 h relative to LPS challenge. Serum was isolated and stored until analyzed for cortisol, cytokines, glucose, non-esterified fatty acids (NEFA), and serum urea nitrogen (SUN) concentrations. Baseline VT was lesser in heifers in the PIS treatment group from -11 to -5 h pre-challenge (treatment x time: P < 0.01) compared to the CON heifers; however, the post-LPS VT response did not differ between treatments (P = 0.89). There was a treatment × time interaction (P < 0.01) for SBS with PIS heifers having lesser SBS from 0.5 to 2 h post-challenge compared to CON. There was a treatment × time interaction (P = 0.03) for cortisol with PIS heifers having greater cortisol at 0.5, 3, 3.5, 5.5 and 6.5 h post-challenge in comparison to CON. There were treatment × time interactions for the post-challenge cytokine responses (P = 0.05). Specifically, PIS heifers had greater TNF-a from 1.5 to 2 h, yet less TNF-a at 3 h than CON (P < 0.01), and PIS heifers had greater IFN-' from 3.5 to 5.5 h post-challenge than CON (P < 0.01). In contrast, IL-6 was less in PIS than CON heifers from 1.5 to 8 h post-challenge (P < 0.001). Serum glucose concentrations were greater in PIS heifers at -1 h, but less at 2, 3 and 5.5 h compared to CON (treatment × time: P < 0.01). Serum NEFA concentrations were greater (P = 0.04) in PIS than CON heifers. There was a treatment × time interaction (P < 0.01) for SUN with PIS heifers having greater concentrations of SUN at -2, -1.5, 2, 3, 6.5 and 24 h than CON. These data clearly demonstrated that multiple low-dose in utero exposures to an endotoxin has lasting physiological and immunological implications when the offspring encounter a similar immunological insult during the postnatal period.