Effects of systemic tumor necrosis factor alpha administration on performance, metabolism, and immune responses...

Systemic inflammation has been linked to an increased risk of postpartum diseases, including mastitis in dairy cows; however, these associations do not necessarily imply a causal relationship. The objective of this study was to evaluate the effects of experimentally induced systemic inflammation on performance, metabolism, and immune responses before and during an intramammary challenge in postpartum dairy cattle. Pregnant, parous dry Holstein cows were blocked by parity, expected calving date, and predicted transmitting ability for milk, and randomly assigned to receive a daily s.c. injection of either recombinant bovine tumor necrosis factor α (rbTNFα; 2 µg/kg BW in 10 mL PBS; n = 10) or saline (control [CON]; 10 mL PBS; n = 10) from d 1 to 7 postpartum. On d 4 postpartum, all cows were challenged intramammarily with Streptococcus uberis (2,500 cfu) in a randomly selected rear quarter. Blood and milk samples (composite and quarter-level foremilk) were collected once daily. Glucose, nonesterified fatty acids (NEFA), BHB, and haptoglobin were measured in plasma. A Luminex, microsphere-based, multiplex assay was used to measure cytokines in plasma and skim milk (defatted via centrifugation). Data were analyzed using linear mixed models including the fixed effects of treatment, time, and their interaction, with block included as a random effect. Cows treated with rbTNFα tended to consume less DM and produced less milk and ECM yields than CON both before and during the intramammary S. uberis challenge. Plasma NEFA concentrations were greater in rbTNFα than CON both before and during the intramammary S. uberis challenge, but no treatment effects were found on plasma BHB or glucose. Cows treated with rbTNFα had greater concentrations of plasma TNFα, macrophage inflammatory protein (MIP)-1α, MIP-1β (h 12-156 following the start of treatments), and haptoglobin (h 36-108) both before and during the intramammary S. uberis challenge. Additionally, cows treated with rbTNFα had greater plasma interleukin (IL)-10 (h 12-156), but lesser plasma IL-36 receptor antagonist both before and during the intramammary S. uberis challenge. Furthermore, cows treated with rbTNFα had reduced plasma interferon-γ concentrations during the S. uberis challenge (h 108-156), but not before the S. uberis challenge. Local mammary immune responses were generally similar between rbTNFα-treated and CON cows. Cows treated with rbTNFα had increased skim milk TNFα, IL-4, and IL-17A concentrations as compared with CON. Nevertheless, rbTNFα administration did not affect composite SCS, quarter-level foremilk SCS, and bacterial counts in milk. In conclusion, cows treated with rbTNFα experienced more systemic inflammation, had greater plasma NEFA concentrations, and had poorer lactational performance. Despite these systemic effects, local mammary gland immune responses to S. uberis were similar between treatment groups. These findings suggest that systemic rbTNFα-induced inflammation may compromise overall performance while only marginally affecting local immune defenses in the mammary gland.