Immunometabolic status and productive performance differences between periparturient Simmental and Holstein dairy cows in response to pegbovigrastim

摘要

In the present study, we aimed to investigate the sideeffects of pegbovigrastim, injected approximately 7 dbefore parturition and on the day of calving, on a panelof plasma biomarkers to evaluate energy, inflammatory,oxidative, and liver function status. We also addressedtreatment responses in different breeds during the transitionperiod. Holstein and Simmental cows were randomlyassigned into 2 groups based on expected calvingdate and according to parity: the treated group (PEG;14 Holstein and 12 Simmental cows) received pegylatedrecombinant bovine granulocyte colony stimulating factor(pegbovigrastim, Imrestor; Elanco Animal Health,Greenfield, IN), and the control group (CTR; 14Holstein and 14 Simmental cows) received saline solution.The PEG or CTR treatments were administeredvia subcutaneous injection in the scapular region atapproximately 7 d (mean 7.80 ± 5.50 d) before expectedparturition and within 24 h after calving. Bloodsamples were collected at −21, −7 (before injection),1, 3, and 28 d relative to calving. Milk production wasrecorded at 7, 15, 21, 30, and 42 d. A mixed model withrepeated measures was fitted to the normalized datausing Proc MIXED of SAS (SAS Institute Inc., Cary,NC). Simmental PEG cows showed higher plasma proteinconcentrations at 1 and 3 d after calving comparedwith Simmental CTR and Holstein PEG cows, whereasno differences were detected between Holstein PEG andCTR cows. Albumin was greater at 1 d in SimmentalPEG compared with Simmental CTR cows. In contrast,γ-glutamyl transferase was higher overall (across breed)in PEG than in CTR. The PEG group had highervalues throughout the postcalving period comparedwith CTR. Cows treated with pegbovigrastim had alsohigher alkaline phosphatase (ALP) activity at 1 and 3d after calving. The Holstein PEG group had higherALP activity at 3 d compared with the Holstein CTRand Simmental PEG groups, and higher ALP at 1 dcompared with the Simmental CTR group. The PEGgroup had higher levels of IL-6 at 3 and 28 d but higherIL-1β only at 28 d after calving compared with theCTR group. Overall, Holstein cows were characterizedby a greater response in the production of inflammationbiomarkers (cytokines, haptoglobin, and ceruloplasmin).In addition, PEG cows had higher values ofzinc at 1 and 3 d after calving compared with CTRcows. The response observed in plasma biomarkers forenergy metabolism and liver functionality after pegbovigrastimtreatment in Simmental and Holstein cowswas not different from that in control cows. However,our data shed light on the different metabolic adaptationsduring the transition period between Simmentaland Holstein cows, characterized by different energy,inflammatory, and oxidative pattern responses. For thefirst time, we have highlighted the effect of pegbovigrastimin maintaining stable cytokine levels duringthe first month after parturition, reflecting greaterregulation of neutrophil recruitment, trafficking, andmaturation during the inflammatory response. Theseresults provide evidence of the immunomodulatory actionof pegbovigrastim around parturition, when dairycows are highly immunosuppressed. At the same time,these data demonstrate that increasing release of cytokinesafter parturition is not linked to exacerbation of asystemic inflammation evaluated based on haptoglobinand ceruloplasmin levels.