Effects of maintaining eucalcemia following immunoactivation in lactating Holstein dairy cows

Abstract

Periparturient hypocalcemia is a common metabolic disorder and it is ostensibly associated with negative health and production outcomes. Acute infection also markedly decreases circulating Ca, but the reasons for and consequences of it on physiological and immunological parameters are unknown. Objectives were to evaluate the effects of maintaining eucalcemia on production, metabolic, and immune variables following an intravenous lipopolysaccharide (LPS) challenge. Twelve multiparous lactating Holstein cows (717 ± 20 kg of body weight; 176 ± 34 d in milk; parity 3 ± 0.2) were enrolled in a study containing 2 experimental periods (P); during P1 (3 d), cows consumed feed ad libitum and baseline values were obtained. At the initiation of P2 (4 d), cows were randomly assigned to 1 of 2 treatments: (1) LPS administered (LPS-Con; 0.5 μg/kg of body weight LPS; n = 6) or (2) LPS administered + eucalcemic clamp (LPS-Ca; 0.5 μg/kg of body weight LPS; Ca infusion; n = 6). Cows were fasted for the first 12 h during P2. After LPS administration, ionized Ca was determined every 15 min for 6 h and every 30 min for an additional 6 h and intravenous Ca infusion was adjusted in LPS-Ca cows to maintain eucalcemia. Blood ionized Ca was decreased 23% for the first 12 h postbolus in LPS-Con cows, and by design, Ca infusion prevented hypocalcemia. To maintain eucalcemia for the 12 h, 13.7 g of Ca was infused. The total Ca deficit (including Ca not secreted into milk) accumulated over the 12 h was 10.4 and 20.2 g for the LPS-Con and LPS-Ca treatments, respectively. Mild hyperthermia (0.8°C) occurred for ~6 h post-LPS administration relative to P1. From 6 to 7 h postbolus rectal temperature from LPS-Ca cows was increased (0.6°C) relative to LPS-Con cows. On d 1 of P2, milk yield decreased (61%) in both treatments relative to P1. Relative to LPS-Con cows, milk yield decreased (15%) in LPS-Ca cows during P2. Overall, circulating LPS-binding protein continuously increased postbolus, and at 24 h LPS-binding protein levels in LPS-Ca cows were increased (80%) relative to LPS-Con cows. During P2, serum amyloid A increased (4-fold) in both treatments relative to P1. Administering LPS initially decreased circulating neutrophils, then cell counts progressively increased with time. Calcium infusion decreased neutrophil counts (40%) from 9 to 12 h postbolus relative to LPS-Con cows. Neutrophil function, as assessed by oxidative burst and myeloperoxidase production, did not differ due to treatment. In summary, maintaining eucalcemia (via intravenous Ca infusion) during an immune challenge appeared to intensify inflammation and adversely affect lactation performance.

Evaluating acute inflammation's effects on hepatic triglyceride content in experimentally induced hyperlipidemic dairy cows in late lactation

“…Perhaps one of the most intriguing results of our study was the markedly different pattern in circulating LBP in response to LPS. In contrast to previous LPS infusion studies, which demonstrate a continuous increase in LBP for ~24 h (Horst et al, 2018(Horst et al, , 2019a(Horst et al, , 2020, we observed an abrupt decrease below baseline values at 12 h after LPS infusion. Interestingly, this decrease occurred concurrently with the NEFA plateau and peak TG concentrations.…”

“…Across species, several well-conserved metabolic alterations are employed during immune activation to meet the energetic requirements of leukocytes (Filkins, 1978;Lanza-Jacoby et al, 1998;McGuinness, 2005), and these have been described in detail in our previous ruminant publications (Kvidera et al, 2017;Horst et al, 2018Horst et al, , 2019aHorst et al, ,b, 2020. In brief, a biphasic response in circulating glucose is observed in response to LPS with an initial period of hyperglycemia followed by hypoglycemia (Kvidera et al, 2017;Horst et al, 2018Horst et al, , 2019a.…”

Review: Relationships between metabolism and neutrophil function in dairy cows in the peripartum period

“…Recent work demonstrates the calcium 'cost' of mounting an inflammatory response to an acute LPS challenge. Using a model analogous to Kvidera et al (2017) for glucose, Horst et al, (2018) showed that in the 12 h after challenge with LPS, blood calcium concentration was reduced by 32%, and maintenance of eucalcemia during that time required infusion of 12 g of Ca, or somewhat more than the typical deficit (8 to 10 g) in a cow recumbent with milk fever. Subclinical hypocalcemia is highly prevalent among periparturient cows and is associated with increased risk of displaced abomasum (Chapinal et al, 2011) and milk production losses (Chapinal et al, 2012) and increased culling risk in early lactation (Roberts et al, 2012).…”

Prolonged, low-grade inflammation in the first week of lactation: Associations with mineral, protein, and energy balance markers, and milk yield, in a clinically healthy Jersey cow cohort

“…Using an induction model of acute inflammation, Kvidera et al (2017) demonstrated that euglycemia could be maintained in lactating cows only when exogenous glucose supply was more than 1 kg within 720 min after an LPS challenge. Intravenous administration of LPS resulted in hypocalcemia in dairy cows (Horst et al, 2020). Daily injections of tumor necrosis factor-α (TNF-α; a proinflammatory cytokine) over a 7-d period (i.e., repeated inflammatory insults) in cows in late lactation increased liver triglyceride accumulation (Bradford et al, 2009).…”

“…Parturition is a high-risk period for immune challenges, during which considerable adaptations in metabolism occur to support lactation. In a lipopolysaccharide challenge model using dairy cows, immune activation has been shown to decrease circulating Ca (Horst et al, 2020), suggesting that an acute inflammatory process can negatively affect the metabolic adaptation of dairy cows in the transition period. Using the liver activity index as the main parameter, Bertoni et al (2008) found that cows with higher indexes had increased concentrations of Ca and Mg in the postpartum period; this could be suggestive of an improved metabolic adaptation process.…”