scholarly journals 111 Changes in proinflammatory cytokines and chemokines in beef steers chronically exposed to endophyte-infected tall fescue seed

2019 ◽  
Vol 97 (Supplement_1) ◽  
pp. 42-43
Author(s):  
Alecia R Brown ◽  
Rebecca K Poole ◽  
McKenzie Lane Jackson ◽  
Matthew H Poore ◽  
Carrie L Pickworth ◽  
...  

Abstract Endophyte-infected tall fescue consumption adversely effects health and immune response. The aim of this study was to evaluate the impact of protein supplementation on cytokine response in steers consuming ergovaline, found in endophyte-infected tall fescue. Thirty-two beef steers were fed a total mixed ration (TMR) and randomly assigned to receive one of four treatments for 56 days: endophyte-free seed (0 ug/kg ergovaline) with either 18% (EF-18; n = 8) or 14% dietary protein (EF-14; n = 8) and endophyte-infected seed (500 ug/ kg ergovaline) with 18% (EI-18; n = 8) or 14% dietary protein (EI-14; n = 8). Blood samples were collected for cytokine analysis on d 28 and d 42 of the feeding period representing when steers vaccinated and boostered for bovine viral diarrhea (BVD) types 1 and 2 and infectious bovine rhinotracheitis (IBR). Cytokine concentrations were evaluated using Quantibody Bovine Cytokine Arrays. Data were analyzed using PROC MIXED of SAS with repeated measures. Statistical significance was determined at P0.05). Interestingly, concentrations of cytokines, IL13 (912±148 vs. 410.9±135 pg/mL) and IL21 (1636.0±295 vs. 629±305 pg/mL), which are involved in chronic inflammatory process were greater (P < 0.05) in EI steer compared to EF steers on d 28 and d 42. Concentrations of chemokine CCL4 and proinflammatory cytokines IFNG and IL-1alpha tended to be greater in EI steers compared to EF steers (P < 0.10). Overall, these data demonstrate that consumption of ergovaline increased proinflammatory cytokines and induced a chronic immune response. Developing a better understanding of overall immunity in cattle exposed to endophyte-infected tall fescue is fundamental to improve cattle health within the beef industry.

2019 ◽  
Vol 97 (10) ◽  
pp. 4160-4170 ◽  
Author(s):  
Rebecca K Poole ◽  
Alecia R Brown ◽  
Matthew H Poore ◽  
Carrie L Pickworth ◽  
Daniel H Poole

Abstract Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue that affects performance; however, little information is available pertaining to its effects on immunity. Recently, it has been shown that supplemental CP can improve performance in weaned steers postvaccination. Thus, the objective of this study was to evaluate the effect of supplemental CP on innate and adaptive immune responses in stocker steers chronically exposed to ergovaline. Angus steers (n = 12 pens; 3 steers/pen) were stratified by weight and assigned to a 2 × 2 factorial arrangement to examine crude protein levels of supplement (14% or 18%) and ergovaline exposure (0 or 185 μg ergovaline/kg BW/d via ground endophyte-free (EF) or endophyte-infected (EI) tall fescue seed, respectively) on immune response. Consumption of low to moderate concentration of ergovaline from EI tall fescue seed was sufficient to induce mild symptoms associated with fescue toxicosis. Blood samples were collected at day 0, 42, and 56 to evaluate infectious bovine rhinotracheitis (IBR) and bovine viral diarrhea virus (BVDV) type 1b titers following vaccine challenge. Additionally, serum cytokine concentrations were evaluated using Quantibody Bovine Cytokine Arrays on day 0, 28, and 42. Data were analyzed using PROC MIXED of SAS with repeated measures. Regardless of treatment, no differences were observed in IBR and BVDV-1b seroconversion following vaccine challenge (P > 0.05). Regardless of crude protein concentration, EI steers had greater concentrations of proinflammatory cytokines (TNF-α, IFN-γ, IL-1α), chemokines (CCL2, CCL4, MIG), anti-inflammatory cytokines (IL-2, -13, -15, -21), and various growth factors (FGF-1, IGF-1, VEGF-A) when compared to EF steers (P < 0.05). Furthermore, VEGF-A and IGF-1 concentrations were greater in EI-14 steers on day 28 compared to EI-18, EF-14, and EF-18 steers (P < 0.05), however, this difference was not observed on day 0 or 42 (P > 0.05). Based on these data, steers exposed to ergovaline have an increase in pro- and anti-inflammatory cytokines and supplemental CP had minimal impact to mitigate this response. However, in the current study, exposure to ergovaline had little to no effect on adaptive immunity and response to vaccination. Together, chronic exposure to ergovaline results in a hyperactive innate immune response, which may lead to an immuno-compromised animal.


2020 ◽  
Vol 98 (Supplement_2) ◽  
pp. 40-40
Author(s):  
Alecia R Brown ◽  
McKenzie L Haimon ◽  
Rebecca Poole ◽  
Matt H Poore ◽  
Daniel H Poole

Abstract Fescue toxicosis is a syndrome common in cattle grazing fescue containing an endophyte that produces ergot alkaloids. Our lab has previously demonstrated that chronic exposure of ergot alkaloids adversely effects innate immune response. Therefore, the objective of this study was to examine changes in cytokine profiles in heat tolerant heifers exposed to ergot alkaloids from endophyte-infected fescue compared to wildtype controls. Angus X Senepol heifers were blocked by weight and hair coat genotype, Slick (S) or Normal (N) then randomly fed novel endophyte fescue (EN) or endophyte-infected fescue (EI) haylage in a total mixed ration for 63d (n=5 per group). Weekly measurements were collected to monitor physiological responses during exposure to ergot alkaloids. Blood samples were collected for cytokine analysis on d 0, 14, 28 and 56. Cytokine concentrations were quantified using Quantibody® Bovine Cytokine Arrays. Data were analyzed using PROC MIXED of SAS with repeated measures. Statistical significance was determined at P&lt; 0.05 and a tendency at 0.05&lt; P&lt; 0.10. Concentrations of TNF were greater in EN-S heifers (6.57 ng/ml) compared to other heifer groups (P&lt; 0.05; 1.33, 2.34, 3.15 ng/ml for EN-N, EI-S, and EI-N, respectively). Concentrations of IL21 were greater in EN-S heifers (8.15 ng/ml) compared to other heifer groups (P&lt; 0.05; 1.55, 3.43, 3.26 ng/ml for EN-N, EI-S, and EI-N, respectively). Concentrations of IFNA (P=0.0543), IFNG (P=0.0558), IL1F1 (P=0.0587), and IL1F5 (P=0.0738) tended to be greater in in EN-S heifers compared to other heifer groups. Interestingly, concentrations of chemokine CCL4 (953.5 vs. 183.7 pg/mL) and CXCL9 (2.57 vs. 0.69 ng/mL) were significantly greater in S heifers than N heifers (P&lt; 0.05). No differences were observed for IL13 and CXCL10 (P &gt;0.05). In contrast to previous data, exposure to ergovaline via endophyte-infected fescue, did not induce an innate immune response. Rather, cytokine concentrations were elevated in heifers with the slick hair genotype. Overall, developing a better understanding of the interaction between ergot alkaloids and the slick hair genotype will help to improve cattle health management.


2019 ◽  
Vol 97 (9) ◽  
pp. 3776-3785 ◽  
Author(s):  
Rebecca K Poole ◽  
Carrisa M Womble ◽  
Matthew H Poore ◽  
Daniel H Poole ◽  
Carrie L Pickworth

Abstract Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue and is detrimental to growth and performance. Recent research has shown that supplementing protein has the potential to enhance growth performance in weaned steers. Therefore, the objective of this study was to evaluate the effect of supplemental CP on physiological parameters in stocker steers experiencing fescue toxicosis. Thirty-six weaned Angus steers (6 mo of age) stratified by weight (196.1 ± 3.6 kg) were assigned to a 2 × 2 factorial arrangement for 56 d: endophyte-free (EF) seed and 14% CP (EF-14; n = 9), EF seed and 18% CP (EF-18; n = 9), endophyte-infected (EI) seed and 14% CP (EI-14; n = 9), and EI seed and 18% CP (EI-18; n = 9). Steer growth and hemodynamic responses were collected weekly during ergot alkaloid exposure. On day 14 of the trial, iButton temperature data loggers were subcutaneously inserted in the lateral neck region to record hourly body temperature for 42 d. Data were analyzed using PROC MIXED of SAS with repeated measures. No differences were observed in DMI, BW, ADG, F:G, or BCS during the treatment period (P > 0.05). Hair shedding scores, rectal temperatures, surface temperatures, and respiration rates were greater in EI steers compared to EF steers regardless of supplemental CP (P < 0.05). However, subcutaneous body temperature was greater in EI-14 steers (37.94 °C) compared to other steer groups (37.60, 37.68, 37.72 ± 0.04 °C for EF-14, EF-18, and EI-18, respectively; P < 0.05). Prolactin concentrations tended to be greater in EF steers when compared to EI steers (P = 0.07). Heart rate and hematocrit were reduced for EI-18 steers compared to other steer groups (P < 0.05). Caudal artery diameter was reduced in EI-18 steers compared to EI-14 steers (2.60 vs. 2.75 ± 0.05 mm, respectively; P < 0.05) and caudal vein diameter was reduced in EI-18 steers (3.20 mm) compared to all other steer groups (3.36, 3.39, 3.50 mm for EF-14, EF-18, and EI-14, respectively; P < 0.05). However, there was no difference observed in systolic or diastolic blood pressure during the treatment period (P > 0.05). Based on the data, exposure to low to moderate levels of ergot alkaloids during the stocker phase had a negative impact on hemodynamic responses and supplemental CP had minimal impact to alleviate symptoms. Therefore, feeding additional protein above established requirements is not expected to help alleviate fescue toxicosis.


2015 ◽  
Vol 100 (6) ◽  
pp. 2214-2222 ◽  
Author(s):  
Jane E. Kerstetter ◽  
Jessica D. Bihuniak ◽  
Jennifer Brindisi ◽  
Rebecca R. Sullivan ◽  
Kelsey M. Mangano ◽  
...  

Context: It has been assumed that the increase in urine calcium (Ca) that accompanies an increase in dietary protein was due to increased bone resorption. However, studies using stable Ca isotopes have found that dietary protein increases Ca absorption without increasing bone resorption. Objective: The objective of the study was to investigate the impact of a moderately high protein diet on bone mineral density (BMD). Design: This was a randomized, double-blind, placebo-controlled trial of protein supplementation daily for 18 months. Setting: The study was conducted at two institutional research centers. Participants: Two hundred eight older women and men with a body mass index between 19 and 32 kg/m2 and a self-reported protein intake between 0.6 and 1.0 g/kg participated in the study. Intervention: Subjects were asked to incorporate either a 45-g whey protein or isocaloric maltodextrin supplement into their usual diet for 18 months. Main Outcome Measure: BMD by dual-energy x-ray absorptiometry, body composition, and markers of skeletal and mineral metabolism were measured at baseline and at 9 and 18 months. Results: There were no significant differences between groups for changes in L-spine BMD (primary outcome) or the other skeletal sites of interest. Truncal lean mass was significantly higher in the protein group at 18 months (P = .048). C-terminal telopeptide (P = .0414), IGF-1 (P = .0054), and urinary urea (P &lt; .001) were also higher in the protein group at the end of the study period. There was no difference in estimated glomerular filtration rate at 18 months. Conclusion: Our data suggest that protein supplementation above the recommended dietary allowance (0.8 g/kg) may preserve fat-free mass without adversely affecting skeletal health or renal function in healthy older adults.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11539-11539
Author(s):  
Suzanne George ◽  
Michael C. Heinrich ◽  
John Raymond Zalcberg ◽  
Sebastian Bauer ◽  
Hans Gelderblom ◽  
...  

11539 Background: Ripretinib is a novel switch-control TKI that broadly inhibits KIT and PDGFRA kinase signaling. In INVICTUS (NCT03353753), a randomized, double-blind, placebo (PBO)-controlled trial of ripretinib in ≥4th-line advanced GIST, ripretinib reduced the risk of disease progression or death by 85% vs PBO with a favorable overall safety profile. Common ( > 20%) adverse events (AEs) included, but were not limited to, alopecia and PPES. Exploratory analyses evaluated the impact of alopecia and PPES on quality of life (QoL). Methods: Patients (pts) with advanced GIST previously treated with at least imatinib, sunitinib, and regorafenib were randomized (2:1) to ripretinib 150 mg QD or PBO. AEs were graded using CTCAE v4 and PROs collected using EQ-5D-5L (EQ5D) and EORTC QLQ-C30 (C30). Repeated measures (RM) models assessed the impact of alopecia and PPES on 5 PROs (EQ5D visual analogue scale; and C30 physical functioning, role functioning, and the overall health and overall QoL questions) within the ripretinib arm. Fixed effects were sex, alopecia/PPES, and ECOG scores at baseline. Results: 128/129 randomized pts received treatment (85 ripretinib 150 mg QD; 43 PBO). Alopecia, regardless of causality, occurred in 44 (51.8%) on ripretinib (34 [40.0%] grade 1; 10 [11.8%] grade 2) and 2 (4.7%) on PBO (both grade 1). PPES occurred in 18 (21.2%) on ripretinib (11 [12.9%] grade 1; 7 [8.2%] grade 2); none on PBO. The median times in days to first occurrence and worst severity grade with ripretinib were 57.0 and 62.5 for alopecia; 56.5 and 57.0 for PPES. The RM models showed a slight trend towards improvement in PRO score over time for pts with alopecia; the only association reaching a P-value of < 0.05 was between alopecia and increased overall QoL. None of the associations between PPES and PRO scores reach P < 0.05. All PRO p-values are nominal, and no statistical significance is being claimed. Conclusions: Ripretinib had a favorable overall safety and tolerability profile. When stratified by alopecia and PPES, patient-reported assessments of function, overall health, and overall QoL were maintained over time. For both alopecia and PPES, onset and maximum severity occurred almost simultaneously, indicating that these events generally did not progressively worsen. These results suggest that alopecia and PPES are manageable and do not have a negative effect on function, overall health, and QoL. Clinical trial information: NCT03353753 .


Gut Pathogens ◽  
2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Esra’a Keewan ◽  
Saleh A. Naser

Abstract Background MiR-146a, an effector mediator, targets Notch-1 and regulates the innate and adaptive immune systems response. Recently, we reported that Notch-1 signaling plays a key role in macrophage polarization and response during infection. We employed Mycobacterium avium paratuberculosis (MAP) infection in Crohn’s disease (CD) as a model to demonstrate the role of Notch-1/IL-6 signaling on MCL-1 based apoptosis and intracellular MAP infection and persistence. This study was designed to investigate the impact of polymorphisms in miR146a on the immune response and infection in our MAP-CD model. Methods We determined the incidence of miR-146a rs2910164 G > C in 42 blood samples from clinical CD patients and controls. We also measured the effect of rs2910164 on expression of Notch-1 and IL-6, and plasma IL-6 protein levels in our study group. Finally, we analyzed the blood samples for MAP DNA and studied any correlation with miR-146a polymorphism. Samples were analyzed for statistical significance using unpaired tow-tailed t-test, unpaired two-tailed z-score and odds ratio. P < 0.05 considered significant. Results MiR-146a rs2910164 GC was detected at a higher incidence in CD (52.6%) compared to healthy controls (21.7%) rs2910164 GC Heterozygous polymorphism upregulated Notch-1 and IL-6, by 0.9 and 1.7-fold, respectively. As expected, MAP infection was detected more in CD samples (63%) compared to healthy controls (9%). Surprisingly, MAP infection was detected at a higher rate in samples with rs2910164 GC (67%) compared to samples with normal genotype (33%). Conclusions The data clearly associates miR-146a rs2910164 GC with an overactive immune response and increases the risk to acquire infection. The study is even more relevant now in our efforts to understand susceptibility to SARS-CoV-2 infection and the development of COVID-19. This study suggests that genetic variations among COVID-19 patients may predict who is at a higher risk of acquiring infection, developing exacerbating symptoms, and possibly death. A high scale study with more clinical samples from different disease groups is planned.


2021 ◽  
Author(s):  
Belen Retamal-Valdes ◽  
Wim Teughels ◽  
Laryssa Macedo Oliveira ◽  
Rebeca Nascimento da Silva ◽  
Aretuza Fritoli ◽  
...  

Abstract Background: The association of scaling and root planing (SRP) with systemic metronidazole (MTZ) plus amoxicillin (AMX) has shown to be an effective treatment protocol, particularly for Periodontitis Stages III and IV, generalized. More recently, probiotics have also been suggested as a promising adjunctive treatment for periodontal diseases due to their antimicrobial and anti-inflammatory properties. Therefore, the aim of this randomized clinical trial (RCT) is to evaluate the clinical, microbiological and immunological effects of probiotics as adjuncts to SRP alone or with MTZ+AMX in the treatment of periodontitis. Methods: Subjects with periodontitis are being randomly assigned to receive (i) SRP alone, or with (ii) two probiotic lozenges/day for 90 days (Prob), (iii) MTZ (400 mg) and AMX (500 mg) thrice a day (TID) for 14 days (MTZ+AMX), or (iv) Prob and MTZ+AMX. Subjects are being monitored for up to 12 months post-treatment. Nine subgingival plaque samples per patient are being collected at baseline and at 3, 6 and 12 months post-therapy, and analyzed by checkerboard DNA–DNA hybridization for 40 bacterial species. Peripheral blood and gingival crevicular fluid (GCF) of four randomly selected periodontal sites will be analyzed by means of a multiplex fluorescent bead-based immunoassay for 17 cyto/chemokines. Statistical analyses: The significance of differences in each group (over the course of the study) will be sought using repeated measures ANOVA or Friedman tests; and among groups (at each time point) using either ANOVA /ANCOVA or Kruskal Wallis tests, depending on normality of the data. The Chi-square test will be used to compare differences in the frequency of subjects achieving the clinical endpoint for treatment (≤4 sites with PD≥5 mm) at 1 year and of self-perceived adverse effects. A stepwise forward logistic regression analysis will be performed in order to investigate the impact of different predictor variables on the percentage of patients achieving the clinical endpoint for treatment. The Number Needed to Treat (NNT) with different treatment protocols will be also calculated. Statistical significance will be set at 5%. Trial registration: ClinicalTrials.gov/NCT03733379/November 7, 2018.


2021 ◽  
Vol 8 ◽  
Author(s):  
Ebenezer Satyaraj ◽  
Arleigh Reynolds ◽  
Robyn Engler ◽  
Jeff Labuda ◽  
Peichuan Sun

Spirulina refers to two species of blue green algae (Arthrospira platensis, and A. maxima) consumed by humans as food for centuries. While, Spirulina has been shown to have immune enhancing properties in several animal and human studies, there are no systematic studies in dogs. The aim of this study was to evaluate the immunomodulatory effect of dietary supplementation with Spirulina in dogs. The study was conducted in two phases: Pre-test (8 wks.) and Test (42 wks.). Thirty adult dogs (mean 2.9 yrs.) were randomized into two groups and fed a nutritionally complete diet in the “Pre-test” phase. At the end of “Pre-test” phase all dogs received a rabies vaccine, and dogs in “test group” were switched to diet supplemented with dried Arthrospira platensis (Spirulina). Response to rabies vaccine was evaluated by Rapid Fluorescent Focus Inhibition Test (RFFIT). Gut immune response was assessed by measuring fecal IgA. Gut microbiota was evaluated by Temporal Temperature Gel Electrophoresis (TTGE) methodology. Repeated measures ANOVA was used to test for differences between groups and statistical significance considered to be p &lt; 0.05. Dogs fed diets supplemented with Spirulina demonstrated enhanced immune status by showing significantly higher vaccine response and higher levels of fecal IgA as compared to the control group. Supplementing diets with Spirulina also resulted in significantly increased gut microbiota stability in the test group. In conclusion, diets supplemented with Spirulina significantly enhanced immune response and gut health in dogs.


Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1751
Author(s):  
Richard J. Bloomer ◽  
Matthew Butawan ◽  
Marie van der Merwe ◽  
Faith H. Keating

Background: Certain dietary fibers have been reported to improve gut health and cellular immunity. Ambrotose is a glyconutrient supplement that contains mannose-rich polysaccharides (acemannan), reported to improve immune function. A more nutrient-dense version of this dietary supplement has been developed recently, with added aloe leaf gel powder (acemannan). The purpose of this study was to evaluate the impact of the traditional and newly developed Ambrotose products on immunity, gut health, and psychological well-being in healthy men and women. Methods: Seventy-five men and women were randomly assigned in double-blind manner to one of five treatments, as follows: Ambrotose Advanced (AA) at 2 or 4 g daily, Ambrotose LIFE (AL) at 2 or 4 g daily, or placebo. Subjects ingested their assigned treatment daily for eight weeks. Resting heart rate, blood pressure, and measures of psychological well-being were analyzed before and after four and eight weeks of supplementation. Blood samples were collected at the same times and analyzed for zonulin, hematology measures, and cytokines—IL-6, IL-10, IL-1β, and TNF-α (analyzed both with and without stimulation via lipopolysaccharide [LPS]). Results: All Ambrotose treatments were well-tolerated. There were no differences among treatments in heart rate or blood pressure across time. Self-reported well-being scores were generally higher for the Ambrotose treatments but there were no changes of statistical significance across time (p > 0.05). Differences of statistical significance were noted for select biochemical variables, the most notable being a dramatic decrease in monocytes in the Ambrotose groups. No change was noted in the cytokine response to LPS stimulation in all groups, indicating a maintenance of a healthy immune response. Conclusion:Regular supplementation with Ambrotose is safe and can improve subclinical cellular adversity (as evidenced by a decrease in monocytes), without unnecessary activation of an immune response.


2001 ◽  
Vol 2001 ◽  
pp. 190-190
Author(s):  
P. H. Robinson ◽  
J. M. Moorby

Considerable effort has recently been directed to better defining protein requirements of dry dairy cows. Early efforts (Moorby et al., 1996) suggested substantial increases in milk and milk protein yield of multiparous cows to a small amount of a high undegradable dietary protein (UDP) supplement in the late dry period. Recent studies have not consistently supported these findings. The objective of this experiment was to define the impact of supplementation of a high UDP supplement in the late dry period of multiparous dairy cows on production of milk and its components.


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