Elevated plasma haptoglobin concentrations following parturition are associated with elevated leukocyte responses and decreased subsequent reproductive efficiency in multiparous Holstein dairy cows

The objectives were to describe the relationship between the intensity of the acute phase response and the metabolic status and leukocyte responses of early postpartum, multiparous cows and determine if subsequent reproductive performance was impaired in cows with a greater acute phase response. Peripheral blood was collected from 240 Holstein cows, 2-8 days in milk and 2nd-8th parity from 8 dairies in Western TX and Eastern NM across 5 days (n = 6 cows/dairy/day). Plasma concentrations of haptoglobin were measured and cows were classified as Low (1st quartile), Moderate (2nd and 3rd quartiles), or High (4th quartile) responders. Metabolic measurements included: plasma glucose, urea nitrogen, non-esterified fatty acids and β-hydroxybutyrate concentrations. Leukocyte response measurements included: total leukocyte counts and differentials, neutrophil surface expression of L-selectin, neutrophil oxidative burst capacity when co-cultured with an environmental Escherichia coli, as well as the secretion of tumor necrosis factor-α and interferon-γ when diluted whole blood were co-cultured with lipopolysaccharide and phytohemagglutinin-P, respectively. All data are reported as Low, Moderate, and High haptoglobin responders. Plasma haptoglobin concentrations ranged from below the limit of detection to 8.4 μg/mL, 8.5 to 458 μg/mL, and 459 to 1757 μg/mL. The High cows had more severe neutropenia (3.45, 3.31, and 2.23 ± 0.31 × 106 cells/mL; P = 0.013) Additionally, the innate leukocyte responses of the High cows were stimulated as evident by increased secretion of tumor necrosis factor-α (568, 565, and 730 ± 73.4 pg/mL; P = 0.003), surface expression of L-selectin on neutrophils (70.8, 71.9, and 119.8 ± 7.9 geometric mean fluorescence intensity; P = 0.001), and greater neutrophil oxidative burst capacity (37.9, 40.4, and 47.9 ± 0.31 geometric mean fluorescence intensity; P = 0.002). In contrast, the secretion of the T-lymphocyte derived cytokine, interferon-γ, was suppressed in both the Moderate and High cows when compared with Low cows (718, 408, and 322 ± 92.2 pg/mL; P = 0.01). Haptoglobin class had an overall effect on days to conception (P = 0.039). The number of days in milk for 75% of the cows in each haptoglobin class to conceive increased from 123 d in the Low group, 139 d in the Moderate group, and 183 d in the High group. These data indicate that a stronger acute phase response during the early postpartum period that is characterized by an activated innate immune system and a suppressed mitogen-induced interferon-γ secretion resulted in impaired reproductive efficiency, and this response was consistent across the large commercial dairy herds sampled.