Abstract
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.
Epigenetic regulation of innate immune memory in microglia
