Heifers (n = 4/genotype) from unselected (stable genotype since 1964, UH) and contemporary (CH) Holsteins that differed in milk yield (6,200 and 11,100 kg milk/305 d) were used to assess the impact of selection on innate immune and acute-phase response to an endotoxin (lipopolysaccharide; LPS). Jugular catheters were implanted 24 h before LPS administration. Blood samples were collected at −1, −0.5, 0, 1, 2, 3, 4, 6, 8, and 24 h relative to iv administration of 0.5 μg LPS/kg BW. Rectal body temperature (BT) was determined at these sampling times and at 5 and 7 h. Dermal biopsies were collected after the 24 h blood sample and processed to isolate fibroblasts. Plasma was analyzed for tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), serum amyloid A (SAA), xanthine oxidase (XO), and nitrate + nitrite (NOx), cortisol, glucose, and IGF-1 content. Isolated fibroblasts were exposed to IL-1β or LPS and IL-6 and IL-8 content of culture media determined. Exposure to LPS increased BTs and plasma concentrations of TNF-α, IL-6 SAA, XO, cortisol, and glucose (P < 0.05) in both genotypes. Plasma concentrations of TNF-α, XO, NOx, and glucose did not differ (P > 0.25) between the genotypes, but IL-6 and SAA concentrations were reduced (P < 0.05) in CH relative to UH heifers while cortisol and IGF-1 concentrations tended (P < 0.08) to be reduced in CH heifers. After 36 h exposure to LPS, concentrations of IL-6 were greater (P < 0.05) in culture media from incubations of CH than UH fibroblasts but concentrations of IL-8 did not differ between genotypes. There was a trend (P = 0.08) for IL-8 concentrations to be reduced in media from CH fibroblasts exposed to IL-1β for 24 h but IL-6 concentrations did not differ between genotypes. Results indicate 50 yr of selection has reduced the robustness of the innate immune and acute-phase response to LPS in the contemporary Holstein heifer.
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Activation of the innate immune system includes an APR which serves to neutralize pathogens and reduce further pathogen invasion. The APR is stimulated by the release of proinflammatory cytokines including TNF-α, IL-1β, and IL-6 from macrophages and monocytes activated at the site of injury or infection [18,19] . The LPS-induced alterations in plasma TNF-α concentrations did not differ between the genotypes but the IL-6 response was reduced in CH heifers. Results from hepatocyte cultures indicate IL-6 is the primary cytokine regulator of acute phase protein synthesis [20,21] . Although primarily regarded as a proinflammatory cytokine, IL-6 is a pleiotropic cytokine that has pro- and anti-inflammatory functions and can affect a variety of processes including immunity, tissue repair, and metabolism [22,23] . The reduced IL-6 response in CH heifers indicates selection has altered the primary cytokine signal for acute phase protein synthesis which could impact the animal's ability to mount, sustain, and regulate an immune response to gram-negative pathogens. This is supported by the reduced production of SAA in the UH heifers.
The authors appreciate the excellent animal care and courteous assistance provided throughout the study by the staff at the University of Minnesota, West Central Research and Outreach Center at Morris. This work was supported in part by the Minnesota Agricultural Experiment Station, Saint Paul and a Grant-in-Aid award (#22965) from the Office of the Vice President for Research, University of Minnesota, Minneapolis.
© 2019 Elsevier Inc.
- Acute-phase response
- Milk genotype