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Effect of anti-inflammatory treatment on systemic inflammation, immune function, and endometrial health in postpartum dairy cows.

ABSTRACT: Systemic inflammation (SI) is increasingly studied in several species because it may be central in many metabolic disturbances and be a risk factor for clinical disease. This proof-of-concept study evaluated the effects of the anti-inflammatory drug meloxicam on markers of SI and energy metabolism, polymorphonuclear neutrophil (PMN) function, and endometritis in clinically healthy postpartum dairy cows. Cows received meloxicam (0.5?mg/kg of body weight; n?=?20) once daily for 4 days (10-13 days postpartum) or were untreated (n?=?22). Blood samples were collected -7, 1, 3, 5, 7, 10, 11, 12, 13, 14, 18, 21, 28, and 35 days relative to calving to measure serum concentrations of metabolic and inflammatory markers. Function of peripheral blood PMN were evaluated at 5, 10, 14, and 21, and proportion of PMN in endometrial cytology were performed at 5, 10, 14, 21, 28 and 35 days postpartum. Meloxicam decreased serum haptoglobin from the second until the last day of treatment, and improved indicators of energy metabolism (lesser ?-hydroxybutyrate and greater insulin-like growth factor-1 during treatment, and greater glucose at the end of treatment than control cows). This improved PMN function at 14 days postpartum, but the endometrial inflammatory status was not affected.

SUBMITTER: Pascottini OB

PROVIDER: S-EPMC7090035 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Effect of anti-inflammatory treatment on systemic inflammation, immune function, and endometrial health in postpartum dairy cows.

Pascottini O Bogado OB Van Schyndel S J SJ Spricigo J F W JFW Carvalho M R MR Mion B B Ribeiro E S ES LeBlanc S J SJ

Scientific reports 20200323 1

Systemic inflammation (SI) is increasingly studied in several species because it may be central in many metabolic disturbances and be a risk factor for clinical disease. This proof-of-concept study evaluated the effects of the anti-inflammatory drug meloxicam on markers of SI and energy metabolism, polymorphonuclear neutrophil (PMN) function, and endometritis in clinically healthy postpartum dairy cows. Cows received meloxicam (0.5 mg/kg of body weight; n = 20) once daily for 4 days (10-13 days ...[more]

PMID: 32251312

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Project description:The objective of this study was to determine the effects of uterine and systemic inflammatory responses to uterine bacterial contamination at calving in dairy cows on the growth and ovulatory outcomes of the first dominant follicle postpartum. Ovulatory capability of the first dominant follicle postpartum was predicted in 53 multiparous cows by using a combination of follicle growth characteristics and circulating estradiol concentrations. Endotoxin levels were assayed in follicular fluid samples that were aspirated the day after ovulatory outcome prediction. Plasma levels of haptoglobin, a proinflammatory acute phase protein, and paraoxonase, a negative acute phase protein were determined. Uterine bacteria and inflammation were evaluated in three uterine fluid samples from each cow collected on the day of calving, the day after follicle aspiration, and at 35 days postpartum. Cows that had a strong initial uterine inflammatory response (robust recruitment of polymorphonuclear leukocytes of ? 35% and cows with uterine pH < 8.5 on the day of calving) were more likely to have an ovulatory first dominant follicle. Follicular fluid endotoxin levels were higher in non-ovulatory cows compared with ovulatory cows. Endotoxin levels in circulation were not different between ovulatory groups but were higher prepartum than on day 7 and 14 postpartum. Systemic inflammation characterized by elevated haptoglobin concentrations was higher in non-ovulatory cows despite similar bacterial contamination and circulating endotoxin levels. Paraoxonase activity in follicular fluid was significantly associated with the paraoxonase activity in plasma, however, plasma paraoxonase concentrations were not different between non-ovulatory and ovulatory cows. Cows with a higher uterine bacterial load on the day of calving had slower ovarian follicle growth. In summary, a robust uterine inflammatory response on the day of calving was positively associated with ovarian function while elevated systemic inflammation during the early postpartum period was negatively associated with the ovulatory status of the first dominant follicle postpartum.

Project description:BackgroundFertility in dairy cows depends on ovarian cyclicity and on uterine involution. Ovarian cyclicity and uterine involution are delayed when there is uterine dysbiosis (overgrowth of pathogenic bacteria). Fertility in dairy cows may involve a mechanism through which the uterine microbiota affects ovarian cyclicity as well as the transcriptome of the endometrium within the involuting uterus. The hypothesis was that the transcriptome of the endometrium in postpartum cows would be associated with the cyclicity status of the cow as well as the microbiota during uterine involution. The endometrium of first lactation dairy cows was sampled at 1, 5, and 9 weeks postpartum. All cows were allowed to return to cyclicity without intervention until week 5 and treated with an ovulation synchronization protocol so that sampling at week 9 was on day 13 of the estrous cycle. The endometrial microbiota was measured by 16S rRNA gene sequencing and principal component analysis. The endometrial transcriptome was measured by mRNA sequencing, differential gene expression analysis, and Ingenuity Pathway Analysis.ResultsThe endometrial microbiota changed from week 1 to week 5 but the week 5 and week 9 microbiota were similar. The endometrial transcriptome differed for cows that were either cycling or not cycling at week 5 and cyclicity status depended in part on the endometrial microbiota. Compared with cows cycling at week 5, there were large changes in the transcriptome of cows that progressed from non-cycling at week 5 to cycling at week 9. There was evidence for concurrent and longer-term associations between the endometrial microbiota and transcriptome. The week 1 endometrial microbiota had the greatest effect on the subsequent endometrial transcriptome and this effect was greatest at week 5 and diminished by week 9.ConclusionsThe cumulative response of the endometrial transcriptome to the microbiota represented the combination of past microbial exposure and current microbial exposure. The endometrial transcriptome in postpartum cows, therefore, depended on the immediate and longer-term effects of the uterine microbiota that acted directly on the uterus. There may also be an indirect mechanism through which the microbiome affects the transcriptome through the restoration of ovarian cyclicity postpartum.

Project description:This study evaluated the effects of treatment with meloxicam (a non-steroidal anti-inflammatory drug), parity, and blood progesterone concentration on the dynamics of the uterine microbiota of 16 clinically healthy postpartum dairy cows. Seven primiparous and 9 multiparous postpartum Holstein cows either received meloxicam (0.5 mg/kg SC, n = 7 cows) once daily for 4 days (10 to 13 days in milk (DIM)) or were untreated (n = 9 cows). Endometrial cytology samples were collected by cytobrush at 10, 21, and 35 DIM, from which the microbiota analysis was conducted using 16S rRNA gene sequence analysis. A radioimmunoassay was used to measure progesterone concentration in blood serum samples at 35 DIM and cows were classified as ˃ 1 ng/mL (n = 10) or ≤ 1 ng/mL (n = 6). Alpha diversity for bacterial genera (Chao1, Shannon-Weiner, and Camargo's evenness indices) were not affected by DIM, meloxicam treatment, parity, or progesterone category. For beta diversity (genera level), principal coordinate analysis (Bray-Curtis) showed differences in microbiota between parity groups. At the phylum level, the relative abundance of Actinobacteria was greater in primiparous than multiparous cows. At the genus level, there was lesser relative abundance of Bifidobacterium, Lactobacillus, Neisseriaceae, Paracoccus, Staphylococcus, and Streptococcus and greater relative abundance of Bacillus and Fusobacterium in primiparous than multiparous cows. Bray-Curtis dissimilarity did not differ by DIM at sampling, meloxicam treatment, or progesterone category at 35 DIM. In conclusion, uterine bacterial composition was not different at 10, 21, or 35 DIM, and meloxicam treatment or progesterone category did not affect the uterine microbiota in clinically healthy postpartum dairy cows. Primiparous cows presented a different composition of uterine bacteria than multiparous cows. The differences in microbiota associated with parity might be attributable to changes that occur consequent to the first calving, but this hypothesis should be investigated further.

Project description:BackgroundMastitis is the most frequent diseases for transition cows. Identification of potential biomarkers for diagnosis of mastitis is important for its prevention. Thus, this study was conducted to investigate blood variables related to lipid metabolism, oxidative stress and inflammation, and serum variables that are related to health in postpartum cows.ResultsSeventy-six healthy Holstein dairy cows at week 4 before calving were selected to collect blood samples from weeks -?4 to 4 weekly relative to calving, respectively. Milk yield and composition were recorded weekly. According to the cut-off of somatic cell counts (SCC) for diagnosis of mastitis, 33 cows with SCC???500,000 cells ml-?1, 20 cows with 200,000 cells ? SCC?<?500,000 cells ml-?1, and 23 cows with SCC?<?200,000 cells ml-?1 were defined as high, middle, and low SCC, respectively. Serum concentrations of ?-hydroxybutyrate were higher (P?<?0.01) during all weeks, and non-esterified fatty acids were higher in high SCC than in low SCC cows from weeks -?3 to 2 relative to calving. Higher serum concentrations of superoxide dismutase (P?<?0.01) and lower malondialdehyde levels (P?<?0.01) in low SCC than in high SCC cows indicate that the latter suffered from oxidative stress. The difference analysis of the three groups suggested that none of the above-mentioned variables can be used as potential prognostic candidates. On the other hand, high SCC cows exhibited higher blood neutrophil to lymphocyte ratio (NLR, P?<?0.01) and platelet to lymphocyte ratio (PLR, P?<?0.01) than low SCC cows, with a higher NLR (P?<?0.01) in middle SCC than in low SCC cows. The high SCC cows had lower levels of anti-inflammatory factors including IL-10 (P?=?0.05), but higher levels of proinflammatory factors such as IL-6 (P?<?0.01), TNF-? (P?<?0.05), and PSGL-1 (P?<?0.01) than low SCC cows.ConclusionsThe significantly different NLR and PLR pre-partum between the middle and low SCC cows suggest their prognostic potential for postpartum mastitis risk.

Dataset Information

Effect of anti-inflammatory treatment on systemic inflammation, immune function, and endometrial health in postpartum dairy cows.

Publications

Effect of anti-inflammatory treatment on systemic inflammation, immune function, and endometrial health in postpartum dairy cows.

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