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

This study evaluated whether administration of lipopolysaccharide (LPS) at each trimester of 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 receive an LPS challenge. On d 0, heifers were fitted with 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) recorded at 0.5 h intervals from −2 to 8 h and at 24 h relative to LPS challenge. Serum was analyzed for cortisol, cytokines, glucose, non-esterified fatty acids (NEFA), and serum urea nitrogen (SUN) concentrations. Baseline VT was lesser in PIS heifers from −11 to −5 h pre-LPS (treatment × time: P < 0.01) compared to the CON; 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-LPS 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-LPS compared to CON. There were treatment × time interactions for the post-LPS cytokine responses (P ≤ 0.05). Specifically, PIS heifers had greater TNF-α from 1.5 to 2 h, yet less TNF-α at 3 h than CON (P < 0.01), and PIS heifers had greater IFN-γ from 3.5 to 5.5 h post-LPS than CON (P < 0.01). In contrast, IL-6 was less in PIS than CON heifers from 1.5 to 8 h post-LPS (P < 0.001). 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 SUN concentrations at −2, −1.5, 2, 3, 6.5 and 24 h than CON. These data demonstrate that in utero exposure to multiple low doses of endotoxin has lasting physiological and immunological effects when the offspring encounter a similar postnatal immunological insult.