Gestational toxemia in lactating sheep is associated with alterations in circulating inflammatory biomarkers

Abstract

Objectives: Gestational toxemia (GT) is a late pregnancy metabolic disease characterized by the disruption of glucose and lipid homeostasis. Metabolic dysregulation leads to hepatic failure and neurological disorders, which frequently result in the death of both the ewe and its lamb/s. The etiopathology of GT is poorly understood. Several risk factors have been identified (e.g. age, number of fetuses, nutritional status, etc.); however, the large individual variability in GT susceptibility suggests that other factors are likely involved. Recently, inflammation has been associated with metabolic diseases both in cows and sheep. Thus, the study objective was to evaluate changes in inflammatory biomarkers between toxemic and healthy sheep. Materials and methods: The current dataset was retrospectively obtained as a subset from a larger experiment (n=334) conducted at a Lacaune sheep high-yield dairy farm (“Granja Cerromonte”, Spain). Within individuals treated for GT (clinically diagnosed based on neurological symptoms), sheep with the highest β-hydroxybutyrate (BHB) blood concentrations were selected (n=9; TOX). Matching healthy controls (n=9; CON) were chosen based on lambing date, lactation number (4±3lactations), and number of carried lambs (2±1born lambs). Body condition parameters were recorded and a fasting blood sample (prior to morning feeding) was collected in late gestation (6±2 days before parturition). Results: There were no differences in body weight or body condition score between groups. As expected, TOX sheep had decreased glucose (58.8 vs. 69.4 mg/dl; P < 0.02), and increased non-esterified fatty acids (1.57 vs. 0.72 mM; P < 0.0004; NEFA) and BHB (2.00 vs. 0.84 mM; P < 0.0004) blood concentrations, compared to CON sheep. Circulating cholesterol was decreased in TOX sheep (83.8 vs. 98.4 mg/dl; P < 0.03); but fructosamine, lactate, triglycerides and urea concentrations did not differ between groups. Gestational toxemia increased circulating tumor necrosis factor α (8.4 vs. 5.9 pg/ml; P < 0.002) and decreased haptoglobin (2.4 vs. 7.1 mg/dl; P < 0.03), but did not change interleukin-6 concentrations. Haptoglobin concentrations were negatively correlated with both BHB (r = -0.62; P < 0.006) and NEFA (r = -0.60; P < 0.009) levels. Tumor necrosis factor α concentrations tended to be and were positively correlated with BHB (r = 0.42; P < 0.09) and NEFA (r = 0.82; P < 0.0001) levels. Conclusions: In summary, GT in sheep appears to be associated with alterations in biomarkers of inflammation.