Administration of LPS Three Times during Gestation Alters the Postnatal Acute Phase and Metabolic Responses to an LPS Challenge in Weaned Beef Heifers

This study evaluated whether three administrations of lipopolysaccharide (LPS) during gestation would alter the acute phase (APR) and metabolic responses to a postnatal LPS challenge in weaned heifers. Pregnant crossbred 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 groups (CON; n=26). From these treatment groups, heifer calves (n = 12 PIS and 11 CON) were identified at weaning (244±3d of age) to subsequently receive an LPS challenge. On d0, heifers were fitted with indwelling vaginal temperature (VT) devices, jugular catheters, and moved into individual stalls. On d1, heifers were challenged i.v. with LPS (0.5 µg/kg BW) at 0h. Blood samples were collected and sickness behavior scores (SBS) were recorded at 0.5h intervals from -2 to 8 and at 24h relative to LPS challenge. Serum was isolated and stored until analyzed for cortisol, cytokines, glucose, NEFA, and urea nitrogen (SUN) concentrations. Vaginal temperature was lesser in heifers in the PIS treatment group from -11 to -5h pre-challenge (trt x time P<0.01) compared to the CON group; however, the post-LPS VT response was similar between treatments (P=0.74). There was a trt x time interaction (P<0.01) for SBS with PIS heifers having lesser SBS from 0.5 to 2h post-challenge. There was a trt x time interaction (P=0.04) for cortisol with PIS heifers having greater cortisol at 0.5, 3, 3.5, and 6.5h post-challenge than CON. There were trt x time interactions for the post-challenge cytokine responses (P≤0.05). Specifically, PIS had greater TNF-α at 2 and 2.5h, yet less TNF-a at 3h than CON (P<0.01), and PIS had greater IFN-γ from 3.5 to 5.5h post-challenge than CON (P<0.01). In contrast, IL-6 was less in PIS than CON heifers from 2 to 8h post-challenge (P≤0.02). Glucose was greater in PIS at -1.5h, but less at 2, 3 and 5.5h compared to CON (TRT x Time P<0.01). Serum NEFA tended (P=0.06) to be greater in PIS than CON heifers. There was a trt x time interaction (P<0.01) for SUN with PIS having greater SUN at -2, -1.5, 2, 3, 6.5 and 24h than CON. Thus, in utero exposure to LPS thrice during gestation reduced sickness behaviors and altered pro-inflammatory cytokine responses. These data suggest that prenatal exposure to LPS has the capability to alter the APR of offspring when presented with a similar challenge at weaning.