Multiparous Holsteins with early postpartum calcium dysregulation have a blunted anti-inflammatory cytokine response

J. A. Seminara, A. Sipka, C. R. Seely, B. Wagner, and J. A. A. McArt

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

Many multiparous cows experience dysregulated blood calcium dynamics in early lactation. This condition, also known as dyscalcemia, is associated with a variety of adverse health and production outcomes. Cytokines are molecules that play essential roles in initiating and resolving systemic inflammation. Our objective in this case-control study was to establish if temporal patterns of cytokines differ between early lactation cows with and without dyscalcemia. We hypothesized that dyscalcemia would be associated with sustained proinflammatory cytokine responses. Multiparous Holstein cows on 2 farms in central New York were enrolled into our study at 1 or 2 d prepartum. Blood was collected at enrollment, for the first 5 DIM, and at 7 and 10 DIM. Samples from 4 DIM were analyzed for total serum calcium concentration (tCa) to classify cows as dyscalcemic (tCa < 2.2 mmol/L) or eucalcemic (tCa ≥ 2.2 mmol/L). Dyscalcemic cows (n = 20) were matched with eucalcemic cows (n = 36) such that the final proportion of dyscalcemic cows in our study would be comparable to the dyscalcemia prevalence on U.S. commercial herds (~35%). Samples from each timepoint were then analyzed using a bead-based multiplex assay for 3 cytokines: tumor necrosis factor-α, interferon-γ, and interleukin (IL)-10. Temporal patterns were compared between groups using linear mixed effects models including the fixed effects of calcium group, DIM, parity group (2, 3, or ≥4), farm, all relevant 2-way interactions, and the random effect of cow. We adjusted for confounding using a common marker of systemic inflammation measured at 4 DIM. We only detected a group effect on the anti-inflammatory cytokine IL-10 (P = 0.01). There was evidence for a group×DIM interaction (P = 0.09), whereby dyscalcemic cows had lower blood concentrations of IL-10 than eucalcemic cows at 3 (P = 0.06), 4 (P = 0.07), 5 (P = 0.008), 7 (P < 0.001), and 10 DIM (P = 0.03). Our study is a preliminary investigation; however, these results suggest that eucalcemic cows may resolve inflammation more effectively than dyscalcemic cows, hinting at a mechanism behind differing outcomes.

Key words: dyscalcemia, inflammation, interleukin-10