Effects of endophyte-infected tall fescue seed and protein supplementation on stocker steers: II. Adaptive and innate immune function

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.

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Effects of endophyte-infected tall fescue seed and protein supplementation on stocker steers: I. Growth performance and hemodynamic responses

Journal of Animal Science ◽

10.1093/jas/skz249 ◽

2019 ◽

Vol 97 (9) ◽

pp. 3776-3785 ◽

Cited By ~ 3

Author(s):

Rebecca K Poole ◽

Carrisa M Womble ◽

Matthew H Poore ◽

Daniel H Poole ◽

Carrie L Pickworth

Keyword(s):

Body Temperature ◽

Growth Performance ◽

Treatment Period ◽

Tall Fescue ◽

Repeated Measures ◽

Negative Impact ◽

Protein Supplementation ◽

Fescue Toxicosis ◽

Hemodynamic Responses ◽

Minimal Impact

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.

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Ivig Negatively Regulates LPS-Induced Monocytes Activation Through a Microrna-146a Related Mechanism

Blood ◽

10.1182/blood.v120.21.3274.3274 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3274-3274

Author(s):

Lionel Loubaki ◽

Renée Bazin

Keyword(s):

Immune Response ◽

Inflammatory Cytokines ◽

Small Rna ◽

Cytokine Production ◽

Innate Immune ◽

Human Monocytes ◽

Monocytic Cells ◽

Tnf Α ◽

Anti Inflammatory ◽

Stimulation Of

Abstract Abstract 3274 Background: Cells from the monocytic lineage are known to play a central role in the immune defense against pathogens. In the adaptive immune response, they act as antigen presenting cells to trigger T and B cell responses. Monocytic cells also participate in innate immunity following recognition of pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharides (LPS), which leads to their activation and release of very potent inflammatory mediators. The innate immune response thus needs to be tightly regulated to control not only its onset, but also its termination in order to avoid excessive inflammation. Recent studies have shown that the differentiation and functions of monocytic cells involve small RNA species, named microRNAs (miRNAs). MiRNAs are 21–23 nucleotide long single strand RNAs, which mainly cause gene silencing by degradation of target mRNAs or by inhibition of translation. Among them, miR-146a has captivated interest as it plays an important role in the negative regulation of acute inflammatory responses during activation of the innate immune system. In fact, it has been shown that miR-146a expression is gradually increased in THP-1 monocytic cells following stimulation with LPS or cytokines (e.g. IL-1β and TNF-α) via a NF-κB dependent pathway. MiR-146a inhibits the expression of IRAK1 and TRAF6 leading to the subsequent suppression of NF-κB activity. Consequently, the expression of NF-κB target genes such as IL-1β, TNF-α and PU.1 is suppressed. Therefore, miR146a controls NF-κB signaling via a negative feedback regulation loop and thus can be considered as an anti-inflammatory mediator. IVIg is a therapeutic preparation of polyclonal human IgG isolated from the plasma of thousands of healthy donors. IVIg is well known for its anti-inflammatory effects on a variety of immune cells and processes. More precisely, it has been shown to abrogate the capacity of monocyte-derived dendritic cells to secrete pro-inflammatory cytokines while increasing the expression of anti-inflammatory cytokines such as IL-10. We thus hypothesize that at least some of the anti-inflammatory effects of IVIg on monocytic cells could be triggered through the modulation of miR-146a expression. Objectives: To evaluate the involvement of miR-146a in the anti-inflammatory effects of IVIg following LPS stimulation of human monocytes. Methods: Human monocytes were obtained from the blood of healthy volunteers and treated with LPS (1 mg/mL) or IVIg (15 mg/mL) alone or alternatively, pretreated with LPS followed by addition of IVIg. Pre-treatment with LPS was done during for 4 h prior to addition of IVIg for 3, 6, 12 and 24 hours. Cells were then recovered and separated in two parts. The first part was used to extract the small RNA fraction of total RNA for miRNA analysis and the second part was used for protein isolation. The miR-146a level was measured by real time PCR while NF-kB and IRF4 protein levels were evaluated by western blotting. Finally, the expression of the transcription factor PU.1 was evaluated by flow cytometry. Results: Our preliminary data revealed that addition of IVIg to LPS-pretreated human monocytes resulted in a significant upregulation of miR-146a expression associated with a significant reduction in NF-κB expression. Furthermore, the expression of the PU.1/IRF4 transcriptional activator complex involved in the stimulation of inflammatory cytokine production was modulated. Indeed, we found that the expression PU.1 was reduced in IVIg-treated cells whereas IRF4 expression was increased, thus promoting the IRF4-mediated cytokine production inhibitory pathway. Conclusion: Our preliminary data suggest that in human monocytes, the anti-inflammatory effects of IVIg may involve miR-146a negative feedback loop regulation of NF-κB activity. Disclosures: No relevant conflicts of interest to declare.

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LL-37 Immunomodulatory Activity during Mycobacterium tuberculosis Infection in Macrophages

Infection and Immunity ◽

10.1128/iai.00936-15 ◽

2015 ◽

Vol 83 (12) ◽

pp. 4495-4503 ◽

Cited By ~ 32

Author(s):

Flor Torres-Juarez ◽

Albertina Cardenas-Vargas ◽

Alejandra Montoya-Rosales ◽

Irma González-Curiel ◽

Mariana H. Garcia-Hernandez ◽

...

Keyword(s):

Immune Response ◽

Inflammatory Cytokines ◽

Innate Immune Response ◽

Transforming Growth Factor ◽

Innate Immune ◽

Immunomodulatory Activity ◽

Interleukin 17 ◽

Host Defense Peptides ◽

Content Type ◽

Anti Inflammatory

Tuberculosis is one of the most important infectious diseases worldwide. The susceptibility to this disease depends to a great extent on the innate immune response against mycobacteria. Host defense peptides (HDP) are one of the first barriers to counteract infection. Cathelicidin (LL-37) is an HDP that has many immunomodulatory effects besides its weak antimicrobial activity. Despite advances in the study of the innate immune response in tuberculosis, the immunological role of LL-37 duringM. tuberculosisinfection has not been clarified. Monocyte-derived macrophages were infected withM. tuberculosisstrain H37Rv and then treated with 1, 5, or 15 μg/ml of exogenous LL-37 for 4, 8, and 24 h. Exogenous LL-37 decreased tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17) while inducing anti-inflammatory IL-10 and transforming growth factor β (TGF-β) production. Interestingly, the decreased production of anti-inflammatory cytokines did not reduce antimycobacterial activity. These results are consistent with the concept that LL-37 can modulate the expression of cytokines during mycobacterial infection and this activity was independent of the P2X7 receptor. Thus, LL-37 modulates the response of macrophages during infection, controlling the expression of proinflammatory and anti-inflammatory cytokines.

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

Journal of Animal Science ◽

10.1093/jas/skz053.095 ◽

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 ◽

...

Keyword(s):

Immune Response ◽

Proinflammatory Cytokines ◽

Tall Fescue ◽

Dietary Protein ◽

Repeated Measures ◽

Statistical Significance ◽

Protein Supplementation ◽

Beef Steers ◽

Cytokine Analysis ◽

The Impact

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.

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Age and Sport Intensity-Dependent Changes in Cytokines and Telomere Length in Elite Athletes

Antioxidants ◽

10.3390/antiox10071035 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1035

Author(s):

Maha Sellami ◽

Shamma Al-muraikhy ◽

Hend Al-Jaber ◽

Hadaia Al-Amri ◽

Layla Al-Mansoori ◽

...

Keyword(s):

Immune Response ◽

Telomere Length ◽

Inflammatory Cytokines ◽

Elite Athletes ◽

Age Groups ◽

Moderate Intensity ◽

Necrosis Factor Alpha ◽

Blood Samples ◽

Tnf Α ◽

Anti Inflammatory

Background: Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes. Methods: In this study, 80 blood samples from consenting elite athletes were collected for anti-doping analysis at an anti-doping laboratory in Italy (FMSI). Participants were divided into three groups according to their sport intensity: low-intensity skills and power sports (LI, n = 18); moderate-intensity mixed soccer players (MI, n = 31); and high-intensity endurance sports (HI, n = 31). Participants were also divided into two age groups: less than 25 (n = 45) and above 25 years old (n = 35). Serum levels of 10 pro and anti-inflammatory cytokines and two antioxidant enzymes were compared in age and sport intensity groups and telomere lengths were measured in their respective blood samples. Results: Tumor necrosis factor-alpha (TNF-α) was the only cytokine showing significantly higher concentration in older athletes, regardless of sport intensity. Interleukin (IL)-10 increased significantly in HI regardless of age group, whereas IL-6 concentration was higher in the older HI athletes. IL-8 showed a significant interaction with sport intensity in different age groups. Overall, significant positive correlations among levels of IL-6, IL-10, IL-8 and TNF-α were identified. The antioxidant catalase activity was positively correlated with levels of TNF-α. Telomere length increased significantly with sport intensity, especially in the younger group. Conclusion: HI had longer telomeres and higher levels of pro- and anti-inflammatory cytokines, suggesting less aging in HI compared to low and moderate counterparts in association with heightened immune response. Investigation of the functional significance of these associations on the health and performance of elite athletes is warranted.

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Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18168538 ◽

2021 ◽

Vol 18 (16) ◽

pp. 8538

Author(s):

Maciej Kwiatek ◽

Tomasz Gęca ◽

Anna Kwaśniewska

Keyword(s):

Immune Response ◽

Inflammatory Cytokines ◽

First Trimester ◽

Normal Pregnancy ◽

Control Group ◽

Study Group ◽

Tnf Α ◽

Cytokine Levels ◽

Anti Inflammatory ◽

Tgf Β1

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.

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Galectin-8 in the onset of the immune response and inflammation

Glycobiology ◽

10.1093/glycob/cwz077 ◽

2019 ◽

Vol 30 (3) ◽

pp. 134-142 ◽

Cited By ~ 4

Author(s):

María V Tribulatti ◽

Julieta Carabelli ◽

Cecilia A Prato ◽

Oscar Campetella

Keyword(s):

Immune Response ◽

Immune Responses ◽

Innate Immune ◽

High Expression ◽

Innate Immune Responses ◽

Inflammatory Disorders ◽

Anti Inflammatory ◽

Potential Use

Abstract Galectins (Gals), a family of mammalian lectins, have emerged as key regulators of the immune response, being implicated in several physiologic and pathologic conditions. Lately, there is increasing data regarding the participation of Galectin-8 (Gal-8) in both the adaptive and innate immune responses, as well as its high expression in inflammatory disorders. Here, we focus on the pro- and anti-inflammatory properties of Gal-8 and discuss the potential use of this lectin in order to shape the immune response, according to the context.

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Extracellular vesicles from human cardiovascular progenitors trigger a reparative immune response in infarcted hearts

Cardiovascular Research ◽

10.1093/cvr/cvaa028 ◽

2020 ◽

Cited By ~ 8

Author(s):

Bruna Lima Correa ◽

Nadia El Harane ◽

Ingrid Gomez ◽

Hocine Rachid Hocine ◽

José Vilar ◽

...

Keyword(s):

Immune Response ◽

Extracellular Vesicles ◽

Inflammatory Cytokines ◽

Nk Cell ◽

Inflammatory Monocytes ◽

Ifn Γ ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Abstract Aims The cardioprotective effects of human induced pluripotent stem cell-derived cardiovascular progenitor cells (CPC) are largely mediated by the paracrine release of extracellular vesicles (EV). We aimed to assess the immunological behaviour of EV-CPC, which is a prerequisite for their clinical translation. Methods and results Flow cytometry demonstrated that EV-CPC expressed very low levels of immune relevant molecules including HLA Class I, CD80, CD274 (PD-L1), and CD275 (ICOS-L); and moderate levels of ligands of the natural killer (NK) cell activating receptor, NKG2D. In mixed lymphocyte reactions, EV-CPC neither induced nor modulated adaptive allogeneic T cell immune responses. They also failed to induce NK cell degranulation, even at high concentrations. These in vitro effects were confirmed in vivo as repeated injections of EV-CPC did not stimulate production of immunoglobulins or affect the interferon (IFN)-γ responses from primed splenocytes. In a mouse model of chronic heart failure, intra-myocardial injections of EV-CPC, 3 weeks after myocardial infarction, decreased both the number of cardiac pro-inflammatory Ly6Chigh monocytes and circulating levels of pro-inflammatory cytokines (IL-1α, TNF-α, and IFN-γ). In a model of acute infarction, direct cardiac injection of EV-CPC 2 days after infarction reduced pro-inflammatory macrophages, Ly6Chigh monocytes, and neutrophils in heart tissue as compared to controls. EV-CPC also reduced levels of pro-inflammatory cytokines IL-1α, IL-2, and IL-6, and increased levels of the anti-inflammatory cytokine IL-10. These effects on human macrophages and monocytes were reproduced in vitro; EV-CPC reduced the number of pro-inflammatory monocytes and M1 macrophages, while increasing the number of anti-inflammatory M2 macrophages. Conclusions EV-CPC do not trigger an immune response either in in vitro human allogeneic models or in immunocompetent animal models. The capacity for orienting the response of monocyte/macrophages towards resolution of inflammation strengthens the clinical attractiveness of EV-CPC as an acellular therapy for cardiac repair.

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Melatonin as an immunomodulator in children with Down syndrome

Pediatric Research ◽

10.1038/s41390-021-01611-6 ◽

2021 ◽

Author(s):

Dean Huggard ◽

Lynne Kelly ◽

Amy Worrall ◽

Eleanor Gallagher ◽

Lida Fallah ◽

...

Keyword(s):

Immune Response ◽

Down Syndrome ◽

Inflammatory Cytokines ◽

Enzyme Linked Immunosorbent Assay ◽

List Type ◽

Tlr4 Expression ◽

Immunomodulatory Effects ◽

Children With Down Syndrome ◽

Anti Inflammatory ◽

Tlr Signalling

Abstract Background Down syndrome (DS) is a disorder characterised by marked immune dysfunction, increased mortality from sepsis, chronic inflammation, increased oxidative stress, sleep disturbance and possibly abnormal endogenous melatonin levels. Melatonin has a myriad of immune functions, and we hypothesised that this therapeutic agent could modulate the innate immune system in this cohort. Methods We investigated neutrophil and monocyte function (CD11b, TLR4 expression by flow cytometry), genes involved in TLR signalling (MyD88, IRAK4, TRIF), the inflammasome (NLRP3, IL-1β), and circadian rhythm (BMAL, CLOCK, CRY) by qPCR, and inflammatory cytokines (IL-2, IL-6, IL-8, IL-18, IL-1β, TNF-α, IFN-γ, IL-10, IL-1ra, VEGF, Epo, GM-CSF) by enzyme-linked immunosorbent assay (ELISA) following immunomodulation with LPS endotoxin and melatonin. 47 children with DS and 23 age- and sex-matched controls were recruited. Results We demonstrated that melatonin has several significant effects by reducing CD11b and TLR4 expression, attenuating TLR signalling, genes involved in the inflammasome and has the potential to reduce LPS-induced inflammatory responses. Conclusions Immunomodulatory effects of melatonin were found in both paediatric cohorts with more marked effects in the children with DS. Melatonin mediates immune response through a wide array of mechanisms and this immunomodulator may buffer the inflammatory response by regulating pro and anti-inflammatory signalling. Impact We highlight that melatonin mediates its immune response through a wide array of mechanisms, its effects appear to be dose dependant and children with Down syndrome may be more receptive to treatment with it. Immunomodulatory effects of melatonin were demonstrated with marked effects in the children with Down syndrome with a reduction of MyD88, IL-1ß and NLRP3 expression in whole-blood samples. Melatonin is a proposed anti-inflammatory agent with a well-established safety profile, that has the potential for mitigation of pro- and anti-inflammatory cytokines in paediatric Down syndrome cohorts, though further clinical trials are warranted.

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