Effect of Pegbovigrastim on Hematological Profile of Simmental Dairy Cows during the Transition Period

Trimboli, Francesca; Morittu, Valeria Maria; Loria, Antonio Di; Minuti, Andrea; Spina, Anna Antonella; Piccioli-Cappelli, F.; Trevisi, Erminio; Britti, Domenico; Lopreiato, Vincenzo

doi:10.3390/ani9100841

Cited by 9 publications

(18 citation statements)

References 33 publications

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“…MPO synthesis is mainly limited to myeloid cells in the bone marrow. The influence of pegbovigrastim on MPO expression, an enzyme stored in azurophilic granules of granulocytes, agreed with increased bone marrow production induced by treatment in the study of Trimboli et al [40]. In this case, our results were opposite those reported by Heiser et al [15] for the same gene, i.e., pegbovigrastim did not upregulate MPO.…”

Section: Discussionsupporting

confidence: 90%

“…In this respect, Rado et al [44] suggested that lactoferrin (involved in several physiological and protective functions, including regulation of iron absorption in the bowel and mainly antimicrobial activities [46]) is synthetized in developing neutrophils during the maturation process and present in secondary granules of PMNs. Thus, the latter could imply that pegbovigrastim was also able to induce neutrophils' maturation (supported also by the greater levels of MPO and LCN2), besides the effect of stimulating the formation of granulocyte colonies from bone marrow-derived precursors [40].…”

Section: Discussionmentioning

confidence: 97%

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Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows

Lopreiato

Palma

Minuti

et al. 2020

Animals

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Pegbovigrastim is a commercial long-acting analog of bovine granulocyte colony-stimulating factor (rbG-CSF) that promotes the increased count and functionality of polymorphonuclear cells in dairy cows around the time of parturition. We hypothesized that pegbovigrastim administered to periparturient cows at approximately seven days before parturition and within 24 hours after calving could affect the profiles of gene networks involved in leukocyte function. Blood was collected on Day 3 after calving from treated groups (pegbovigrastim (PEG); 13 Simmental (seven multiparous and six primiparous) and 13 Holstein (seven multiparous and six primiparous) cows) that received pegbovigrastim (Imrestor; Elanco Animal Health) and controls (CTR; 13 Simmental (seven multiparous and six primiparous) and 13 Holstein (six multiparous and seven primiparous) cows) that received saline solution. Blood from all cows was sampled from the jugular vein in a PAXgene Blood RNA System tube (Preanalytix, Hombrechtikon, Switzerland) for RNA extraction. The RT-qPCR analysis was performed to investigate a panel of 34 genes of interest, representing recognition, immune mediation, migration, cell adhesion, antimicrobial strategies, inflammatory cascade, oxidative pattern, and leukotrienes in whole blood leukocytes. Normalized data were subjected to the MIXED model of SAS (ver. 9.4) with treatment, breed, parity, and their interaction as fixed effects. Compared with CTR, whole blood leukocytes of PEG cows had higher expression of genes involved in recognition and immune modulation (CD14, CD16, MYD88, TLR2, and TLR4), cell adhesion (ITGB2, ITGAL, TLN1, SELL, SELPLG, and CD44), antimicrobial activity (MMP9, LTF, and LCN2), and inflammatory cascade (CASP1, TNFRSF1A, IL1B, IL1R, IL18, IRAK1, NLRP3, and S100A8). This suggested an improvement of migration, adhesion, and antimicrobial ability and an enhanced inflammatory response, which in turn could trigger immune cell activation and enhance function. Expression of SOD2 and ALOX5 was also greater in the PEG group. In contrast, compared with CTR cows, PEG led to lower expression of RPL13A, ALOX15, IL8, and TNF. Overall, leukocytes from Simmental compared with Holstein cows had greater expression of IDO1, RPL13A, ALOX5, CD44, CX3CR1, ITGB2, and TNFA, whereas expression of CD16 and TLR2 was lower. Overall, compared with multiparous cows, primiparous cows had higher expression of IL1B, IL18, MYD88, SELL, and TLR2 and lower expression of MMP9. Simmental cows seemed more sensitive to induction of the immune system after calving, as revealed by the greater abundance of genes involved in immune system adaptation, regardless of pegbovigrastim treatment. Primiparous cows undergoing a new stress condition with respect to older cows were characterized by leukocytes with a higher inflammatory response. In conclusion, pegbovigrastim led to higher expression levels of most genes involved in the processes investigated, suggesting a thorough activation of the immune machinery during the critical post-partum period.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 97%

Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows

Lopreiato

Palma

Minuti

et al. 2020

Animals

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“…Pegfilgrastim is most widely used synthetic immunostimulant of G-CSF production [ 103 ]. In agriculture, a bovine G-CSF or its inducer pegbovigrastim are administered to cattle prior to parturition to boost the immune system and decrease the incidence of mastitis [ 104 , 105 , 106 ].…”

Section: Alternative Strategies To Combat Antibiotic Resistancementioning

confidence: 99%

Antibiotics in Food Chain: The Consequences for Antibiotic Resistance

2020

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Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant bacterial infections, thereby posing a tremendous threat to public health. The goal of our review is to advance the understanding of mechanisms of dissemination and the development of antibiotic resistance genes in the context of nutrition and related clinical, agricultural, veterinary, and environmental settings. We conclude with an overview of alternative strategies, including probiotics, essential oils, vaccines, and antibodies, as primary or adjunct preventive antimicrobial measures or therapies against multidrug-resistant bacterial infections. The solution for antibiotic resistance will require comprehensive and incessant efforts of policymakers in agriculture along with the development of alternative therapeutics by experts in diverse fields of microbiology, biochemistry, clinical research, genetic, and computational engineering.

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“…Several studies have shown that in cattle, the administration of Pegbovigrastim provides a well-tolerated approach to overcoming periparturient immune suppression, making it possible to restore normal neutrophil function [ 62 , 75 ]. The administration of Pegbovigrastim induces a state of neutrophilia, characterized by a ‘left-shift’ towards progenitor cells with a release of mature neutrophils and band cells from storage pools in bone marrow [ 76 , 77 ]. Pegbovigrastim is found to induce a slight decrease of red cell count and hematocrit in cows treated 7 and 21 days after calving [ 62 , 77 ].…”

Section: Another Drug: Pegbovigrastimmentioning

confidence: 99%

“…The administration of Pegbovigrastim induces a state of neutrophilia, characterized by a ‘left-shift’ towards progenitor cells with a release of mature neutrophils and band cells from storage pools in bone marrow [ 76 , 77 ]. Pegbovigrastim is found to induce a slight decrease of red cell count and hematocrit in cows treated 7 and 21 days after calving [ 62 , 77 ]. The finding of normocytic, hypochromic anemia in 50% (8/16) and 19% (3/16) of the Pegbovigrastim treated and control cows, respectively, could indicate an increased anemic effect after treatment with this immune stimulant [ 77 ].…”

Section: Another Drug: Pegbovigrastimmentioning

confidence: 99%

Outcomes from Experimental Testing of Nonsteroidal Anti-Inflammatory Drug (NSAID) Administration during the Transition Period of Dairy Cows

Trimboli

Ragusa

Piras

et al. 2020

Animals

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During the transition period, dairy cows experience great physiological stress caused by changes in metabolism and in the immune and endocrine systems. A pro-inflammatory state is another difficulty faced by even apparently healthy animals. The most significant negative consequences of inflammation in dairy cows are substantial impairment of milk production and deleterious effects on cows’ health in extreme cases. Nonetheless, a certain degree of inflammation is necessary to sustain physiological adaptations. In recent years, many studies have attempted to determine whether the use of nonsteroidal anti-inflammatory drugs (NSAID) in the transition period of dairy cows could positively affect milk production and cows’ health by controlling the inflammation status. This literature indicates that NSAIDs that act as preferential inhibitors of cyclooxygenase-1 (COX-1) activity show important side effects (e.g., increased risk of retained placenta, culling, or metritis) even if milk production is, on average, ameliorated. In contrast, preferential inhibitors of cyclooxygenase-2 (COX-2) activity have overall positive effects on cows’ health, with potential beneficial effects on milk production. Furthermore, it is important to note that with certain NSAID treatments, milk discarding is mandatory to prevent contamination with drug residues, but increased milk production can compensate for the loss of milk revenue during the withdrawal period.

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Effect of Pegbovigrastim on Hematological Profile of Simmental Dairy Cows during the Transition Period

Cited by 9 publications

References 33 publications

Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows

Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows

Antibiotics in Food Chain: The Consequences for Antibiotic Resistance

Outcomes from Experimental Testing of Nonsteroidal Anti-Inflammatory Drug (NSAID) Administration during the Transition Period of Dairy Cows

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