Intravenous lipopolysaccharide challenge in early versus mid-lactation dairy cattle. II: The production and metabolic responses

Most immunometabolic research utilizes mid-lactation (ML) cows. Cows in early lactation (EL) are in a presumed state of immune suppression/dysregulation and less is known about how they respond to a pathogen. Study objectives were to compare the production and metabolic responses to i.v. lipopolysaccharide (LPS) and to differentiate between the direct effects of immune activation and the indirect effects of illness-induced hypophagia in EL and ML cows. Cows in EL (n = 11; 20 ± 2 d in milk) and ML (n = 12; 131 ± 31 d in milk) were enrolled in a 2 × 2 factorial design containing 2 experimental periods (P). During P1 (3 d), cows were fed ad libitum and baseline data were collected. At the initiation of P2 (3 d), cows were randomly assigned to 1 of 2 treatments by lactation stage (LS): (1) EL (EL-LPS; n = 6) or ML (ML-LPS; n = 6) cows administered i.v. a single bolus of 0.09 µg LPS/kg of body weight; Escherichia coli O55:B5 or (2) pair-fed (PF) EL (EL-PF; n = 5) or ML (ML-PF; n = 6) cows administered i.v. saline. Administering LPS decreased dry matter intake (DMI) and this was more severe in EL-LPS than ML-LPS cows (34 and 11% relative to baseline, respectively). By design, P2 DMI patterns were similar in the PF groups compared with their LPS counterparts. Milk yield decreased following LPS (42% on d 1 relative to P1) and despite an exacerbated decrease in EL-LPS cows on d 1 (25% relative to ML-LPS), remained similar between LS from d 2–3. EL-LPS had increased milk fat content, but no difference in protein and lactose percentages compared with ML-LPS cows. Further, cumulative ECM yield was increased (21%) in EL-LPS compared with ML-LPS cows. During P2, EL-LPS cows had a more intense increase in milk urea nitrogen (MUN) and blood urea nitrogen (BUN) than ML-LPS and EL-PF cows. Administering LPS did not cause hypoglycemia in either EL-LPS or ML-LPS cows, but glucose was increased (33%) in EL-LPS compared with EL-PF. Hyperinsulinemia occurred post-LPS, and insulin was further increased in ML-LPS than EL-LPS cows (2.2-fold at 12 h peak). During P2, circulating glucagon increased only in EL-LPS cows (64% relative to all other groups). Both EL groups had increased NEFA at 3 and 6 h post-LPS from baseline (56%), but NEFA in EL-LPS cows gradually returned to baseline thereafter and were reduced relative to EL-PF until 36 h (50% from 12 to 24 h). Alterations in β-hydroxybutyrate (BHB) did not differ between ML groups, but EL-LPS had reduced BHB compared with EL-PF from 24 to 72 h (51%). Results indicate that there are distinct LS differences in the anorexic and metabolic responses to immune activation. Collectively, EL cows are more sensitive to the catabolic effects of LPS than ML cows, but these exacerbated metabolic responses appear coordinated to fuel an augmented immune system while simultaneously supporting milk synthesis.