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Topic:Cytokines
Cytokines are small proteins that are important in cell signaling and are produced by various cell types in horses, particularly during immune responses. These molecules facilitate communication between cells and play a role in regulating inflammation, immune function, and hematopoiesis. In horses, cytokines are involved in numerous physiological and pathological processes, including infection, inflammation, and wound healing. Examples of cytokines studied in equine research include interleukins, interferons, and tumor necrosis factors. Their expression levels can change in response to disease states, making them potential biomarkers for assessing equine health and disease progression. This page compiles peer-reviewed research studies and scholarly articles that explore the role, regulation, and clinical implications of cytokines in equine health.
Platelet-Rich Products and Their Application to Osteoarthritis. Autologous platelet-rich plasma (PRP) is a biological preparation made from the patient's own plasma that contains a platelet concentration above the whole blood baseline. Owing to the release of growth factors and other cytokines after degranulation, platelets have a central role in inflammation and in different stages of the healing process. For this reason, PRP-derived products have been used to enhance healing of musculoskeletal injuries and modulate progression of inflammatory processes, including osteoarthritis (OA). Osteoarthritis is one of the main causes of musculoskeletal disabilitie...
The Contribution of Specific and Nonspecific Biomarkers in Diagnosis of Equine Gastric Ulcer Syndrome (EGUS) Under Field Condition. The aim of this study is to investigate the diagnostic efficiency of gastrin, pepsinogen, proinflammatory cytokines (TNF-α, IL-6), and oxidative stress biomarkers in horses with equine gastric ulcer syndrome (EGUS). Thirty horses diagnosed with gastroscopic EGUS and 15 clinically healthy horses were selected for this study. The serum levels of gastrin, pepsinogen showed nonsignificant changes in horses with EGUS when compared with healthy horses. The serum levels of TNF-α, IL-6 revealed a significant increase in horses with EGUS when compared with healthy ones. Oxidative stress is evident in...
Effect of injected dexamethasone on relative cytokine mRNA expression in bronchoalveolar lavage fluid in horses with mild asthma. Mild equine asthma is a common inflammatory airway disease of the horse. The primary treatment of mild equine asthma is corticosteroids. The purpose of this study was to investigate the effects of injected dexamethasone on relative IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-17, IL-23, IFN-γ, Eotaxin-2 and TNF-α mRNA expression in bronchoalveolar lavage (BAL) fluid in healthy Thoroughbred horses (n = 6), and those with mild equine asthma (n = 7). Results: Horses with mild equine asthma had a significantly greater bronchoalveolar lavage mast cell percentage than healthy horses...
Autologous bone marrow mononuclear cells modulate joint homeostasis in an equine in vivo model of synovitis. Osteoarthritis (OA) is characterized by macrophage-driven synovitis. Macrophages promote synovial health but become inflammatory when their regulatory functions are overwhelmed. Bone marrow mononuclear cells (BMNCs) are a rich source of macrophage progenitors used for treating chronic inflammation and produce essential molecules for cartilage metabolism. This study investigated the response to autologous BMNC injection in normal and inflamed joints. Synovitis was induced in both radiocarpal joints of 6 horses. After 8 h, 1 inflamed radiocarpal and 1 normal tarsocrural joint received BMNC injec...
Inflammatory mediators are potential biomarkers for extracorporeal shockwave therapy in horses. Extracorporeal shockwave therapy (ESWT) can potentially mask painful injuries in equine athletes. Tests to detect whether a horse has received ESWT prior to competition are needed. Extracorporeal shockwave therapy is known to affect inflammatory mediators in other species, and if these mediators are altered in the horse, these could serve as biomarkers of ESWT. Objective: To test the hypothesis that a single application of ESWT will alter the circulating protein concentrations of 10 inflammatory mediators in horse plasma. Methods: Prospective repeated measures experimental study. Methods: Elev...
Uterine cervix as a fundamental part of the pathogenesis of pregnancy loss associated with ascending placentitis in mares. Anatomical and molecular changes in the cervical barrier in women are a fundamental part of the pathogenesis of pregnancy loss associated with chorioamnionitis. However, there is little information regarding changes in the cervix associated with ascending infection in pregnant mares. To better characterize morphological and molecular changes in the cervix during placentitis, we examined full thickness histology and mRNA expression for a number of inflammatory and endocrine factors in the mucosa and stroma of the cervix of mares (n = 5) after experimental induction of placentitis via transc...
Development of the equine gut microbiota. Shortly after birth the mammalian gut is colonized, by a transient microbiota, highly susceptible to environment and diet, that eventually stabilizes and becomes the resident gut microbiota. In a window of opportunity during the colonization, oral tolerance is established towards resident bacteria. In this study, the development of the equine gut microbiota was investigated in ten foals from parturition until post weaning. We found great differences in the core species of the gut microbiota composition between time-matched samples on Day 7 and 20 post-partum. Between day 20 and Day 50 post-par...
The feto-maternal immune response to equine placentitis. Ascending placentitis is one of the leading causes of abortion in the horse. Minimal work has focused on its effect on fetal fluids or the antenatal immune response of the fetus. Placentitis was induced via transcervical inoculation of Streptococcus equi ssp Zooepidemicus, and fluids/serum/tissues were collected 4-6 days later following euthanasia. Cytokine concentrations were detected using a multiplex immunoassay within fetal fluids (amniotic and allantoic) and serum (maternal and fetal) in inoculated and control mares. In addition, tissues from fetal (spleen, liver, lung, umbilicus, amnioa...
Anti-Inflammatory State in Arabian Horses Introduced to the Endurance Training. Development of an anti-inflammatory state during physical training has been postulated in both human and equine athletes, but it is not completely understood. The aim of this study was to investigate whether endurance training changes pro- and anti-inflammatory cytokine profiles within a 20-week training season in young inexperienced endurance horses. Nine Arabian horses were examined in this prospective 20-week follow-up study. Blood samples were analysed 5 times monthly, at rest and after training sessions. Routine haematological examinations were performed. Cytokine patterns including IL-1...
Analysis of caecal mucosal inflammation and immune modulation during Anoplocephala perfoliata infection of horses. Anoplocephala perfoliata is the commonest equine tapeworm, the adult parasites are attached in groups close to the ileocaecal valve causing marked inflammatory pathology. This work aimed to characterize the nature of the in vivo mucosal immune response to A perfoliata, and to investigate the role of A perfoliata excretory-secretory components in modulating in vitro immune responses. Real-time PCR detected elevation of IL13 and TGFβ transcription in early-stage A perfoliata infection. In late-stage infection, IL-13, IL4 and Ifn transcripts were reduced while the regulatory cytokines, TGFβ...
Microfluidic nutrient gradient-based three-dimensional chondrocyte culture-on-a-chip as an in vitro equine arthritis model. In this work, we describe a microfluidic three-dimensional (3D) chondrocyte culture mimicking in vivo articular chondrocyte morphology, cell distribution, metabolism, and gene expression. This has been accomplished by establishing a physiologic nutrient diffusion gradient across the simulated matrix, while geometric design constraints of the microchambers drive native-like cellular behavior. Primary equine chondrocytes remained viable for the extended culture time of 3 weeks and maintained the low metabolic activity and high Sox9, aggrecan, and Col2 expression typical of articular chondrocytes...
pH-dependent effects of procaine on equine gamete activation†. Procaine directly triggers pH-dependent cytokinesis in equine oocytes and induces hypermotility in stallion spermatozoa, an important event during capacitation. However, procaine-induced hyperactivated motility is abolished when sperm is washed to remove the procaine prior to sperm-oocyte co-incubation. To understand how procaine exerts its effects, the external Ca2+ and Na+ and weak base activity dependency of procaine-induced hyperactivation in stallion spermatozoa was assessed using computer-assisted sperm analysis. Percoll-washed stallion spermatozoa exposed to Ca2+-depleted (+2 mM EGTA) p...
Randomised study of the immunomodulatory effects of azithromycin in severely asthmatic horses. Neutrophilic inflammation is believed to contribute to the airway obstruction and remodelling in equine asthma. Azithromycin, an antibiotic with immunomodulatory properties, reduces pulmonary neutrophilia and hyper-responsiveness in human asthmatics and decreases airway remodelling in rodent models of asthma. It was therefore hypothesised that azithromycin would improve lung function, mucus accumulation and central airway remodelling by decreasing luminal neutrophilia in severe equine asthma. The effects of a 10-day treatment with either azithromycin or ceftiofur, an antimicrobial without immu...
Comparative Anti-inflammatory Effects of Insulin and Flunixin on Acute-Phase Responses and Cardiovascular Biomarkers During Inflammatory Phase in Miniature Donkeys. The objective of this study was to comparatively evaluate the anti-inflammatory effects of intravenous administration of insulin (in different doses) and flunixin on physiological variables, acute-phase responses, and cardiovascular biomarkers during inflammatory phase which was induced by Escherichia coli lipopolysaccharide (LPS) serotype O55:B5 in miniature donkeys. A total of twenty-four clinically healthy male adult miniature donkeys aged 5 ± 1 year and weighing 120 ± 10 kg were studied. The animals were assigned randomly to four experimental groups (three treatment and one positive co...
Plasma Apelin Concentration in Exercised Horses: Preliminary Study. Physical effort is one of the key aspects of keeping horses in good condition. The condition of the animal is reflected by multiple blood parameters. The newly discovered cytokine-apelin can pose one of them, however, so far, has not been studied in the horse population. Apelin is produced by adipocytes and myocytes and plays an important role in the energy metabolism of the body through the influence, for example, on the process of adipogenesis and lipolysis. The aim of this study was to investigate if physical effort of various intensity affects the plasma concentration of apelin in horses. ...
Effect of proinflammatory cytokines on endometrial collagen and metallopeptidase expression during the course of equine endometrosis. Equine endometrosis (endometrial fibrosis) is a degenerative chronic process that occurs in the uterus of the mare and disturbs proper endometrial function. Fibrosis is attributed to excessive deposition of extracellular matrix (ECM) components. The turnover of ECM is mediated by matrix metallopeptidases (MMP). Previously, it was shown that cytokines modulate MMP expression in other tissues and may regulate fibrosis indirectly by attracting inflammatory cells to the site of inflammation and directly on various tissues. However, the regulation of MMP expression in equine endometrosis is still r...
Metalloproteinases and their Inhibitors under the Course of Immunostimulation by CPG-ODN and Specific Antigen Inhalation in Equine Asthma. Inhalation of immunostimulatory bacterial DNA segments (cytosine-phosphate-guanosine-oligodeoxynucleotides, CpG-ODN) normalizes clinical and cytologic parameters in severe equine asthma. We hypothesized that CpG-ODN inhalation also reduces the misbalance of elastinolytic activity in asthmatic horses. Methods: Twenty asthmatic horses diagnosed by clinical examinations using a scoring system were included. All horses inhaled CpG-ODNs for 14 days in 2-day intervals. Matrix metalloproteinase (MMP-2/-9) and tissue inhibitors of metalloproteinase (TIMP-1/-2) concentrations were measured in tracheal ...
Age-related dynamics of pro-inflammatory cytokines in equine bronchoalveolar lavage (BAL) fluid and peripheral blood from horses managed on pasture. The objectives of this study were to evaluate the natural age-related variation and compare the level of pro-inflammatory cytokines in the peripheral blood and lower airways of horses. The mRNA expression of IL-1β, IL-6, IL-8 TNF-α TLR-4 in bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMC) were studied by quantitative real time polymerase chain reaction (PCR) and differential cell count cytology from 44 horses of different ages. A significant age-related increase was found for the mRNA expression of IL-6, IL-8, TLR-4 and TNF-α in stimulated BAL cells and for T...
Effects of allergen-specific immunotherapy on peripheral blood regulatory T cells and serum concentrations of cytokines and immunoglobulins in horses with allergic dermatitis. The aim of this study was to assess the effect of allergen-specific immunotherapy (ASIT) on the immunological responses of horses. Blood samples were taken from thirty-two horses with allergic dermatitis treated with ASIT and 10 healthy control horses at 0, 3, 6, 9 and 12 months to investigate the evolution of the percentage of regulatory T cells (Treg) in the peripheral blood and the serum levels of cytokines and immunoglobulins. Clinical improvement was appreciated by the majority of the horses' owners (56.6%). No effect of ASIT on CD4CD25 Treg cells was found during the one year treatment...
Impact of body weight gain on hepatic metabolism and hepatic inflammatory cytokines in comparison of Shetland pony geldings and Warmblood horse geldings. Non-alcoholic fatty liver disease is known as determining part of human obesity. The impact of body weight (BW) gain on liver metabolism has not been extensively investigated yet. Objective: To investigate hepatic alterations caused by increasing BW in ponies and horses. Methods: A total of 19 non-obese equines (10 Shetland ponies, geldings; nine Warmblood horses, geldings). Methods: Animals received 200% of their metabolizable maintenance energy requirements for 2 years. Serum alkaline phosphatase, glutamate dehydrogenase (GLDH), aspartate aminotransferase (AST), and gamma-glutamyl transferas...
Alteration of the mare’s immune system by the synthetic progestin, altrenogest. Progestins are immunomodulatory in a variety of species. In the horse, the most commonly administered synthetic progestin is altrenogest (ALT), but its effect on the immune system of the non-pregnant mare is unknown. Peripheral blood mononuclear cells (PBMCs) from diestrous mares were incubated with varying concentrations of progesterone (P4) or ALT to assess intracellular production of IFNγ and the expression of select cytokines. Additionally, ten mares received either ALT or VEH daily utilizing a switchback design beginning on the day of ovulation and continuing for 7 days. Circulating PBM...
Evaluation of the effect of experimentally induced cartilage defect and intra-articular hyaluronan on synovial fluid biomarkers in intercarpal joints of horses. Inflammatory and degenerative activity inside the joint can be studied in vivo by analysis of synovial fluid biomarkers. In addition to pro-inflammatory mediators, several anabolic and anti-inflammatory substances are produced during the disease process. They counteract the catabolic effects of the pro-inflammatory cytokines and thus diminish the cartilage damage. The response of synovial fluid biomarkers after intra-articular hyaluronan injection, alone or in combination with other substances, has been examined only in a few equine studies. The effects of hyaluronan on some pro-inflammatory m...
Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect. Equine asthma represents a naturally occurring animal model for human allergic neutrophilic asthma. Inhalative nanoparticle-bound cytosine-phosphate-guanosine (CpG-GNP) immunotherapy, independent of specific allergens, has already shown promising clinical and immunological results in previous studies and offers the possibility to treat the underlying cause of the disease. This study analyses the relationship between dose and response, and evaluates a possible long-term effect. In the prospective, randomised, double-blind clinical field study, 29 horses suffering from equine asthma received 10 ...
Equine placentitis is associated with a downregulation in myometrial progestin signaling†. The current study aimed to elucidate the mechanisms underlying myometrial activation during equine placentitis related to progestogens and the progesterone receptor signaling pathways. Placentitis was induced via intracervical inoculation with Streptococcus equi ssp zooepidemicus in mares at approximately 290 days of gestation (placentitis group; n = 6) with uninoculated gestationally matched mares as controls (n = 4). Mares in the placentitis and control groups were euthanized, and myometrial samples were collected from two regions: region 1-parallel to active placentitis lesion with plac...
Adipose tissue dysfunction in obese horses with equine metabolic syndrome. Obesity is a common feature of equine metabolic syndrome (EMS). In other species, obese adipose tissue shows pathological features such as adipocyte hypertrophy, fibrosis, inflammation and impaired insulin signalling all of which contribute to whole body insulin dysregulation. Such adipose tissue dysfunction has not been investigated in horses. Objective: To determine if obese horses with EMS have adipose tissue dysfunction characterised by adipocyte hypertrophy, fibrosis, inflammation and altered insulin signalling. Methods: Cross-sectional post-mortem study. Methods: Samples of peri-renal (v...
Recombinant horse interleukin-4 and interleukin-10 induced a mixed inflammatory cytokine response in horse peripheral blood mononuclear cells. Interleukin (IL)-4 and IL-10 activate plethora of immune cells and induce the humoral immune response. However, recombinant version of horse IL-4 and IL-10 has not been investigated to understand their immunomodulating activities. This study aimed to produce recombinant horse mature IL-4 and IL-10 in . Immune-modulating activities of recombinant horse IL-4 and IL-10 were investigated in peripheral blood mononuclear cells (PBMCs). Methods: Equine PBMCs were stimulated with recombinant IL-4 and IL-10. A proliferation of PBMCs was measured by XTT assay and cytokines induction was measured by enzy...
Insights into animal models for cell-based therapies in translational studies of lung diseases: Is the horse with naturally occurring asthma the right choice? Human asthma is a widespread disease associated with chronic inflammation of the airways, leading to loss of quality of life, disability and death. Corticosteroid administration is the mainstream treatment for asthmatic patients. Corticosteroids reduce airway obstruction and improve quality of life, although symptoms persist despite treatment in many patients. Moreover, available therapies failed to reverse the lung pathology present in asthma. Animal models, mostly rats and mice, in which the disease is experimentally induced, have been studied to identify new therapeutic targets for human as...
Association of sustained supraphysiologic hyperinsulinemia and inflammatory signaling within the digital lamellae in light-breed horses. Hyperinsulinemia is associated with equine laminitis, and digital lamellar inflammation in equine metabolic syndrome-associated laminitis (EMSAL) is modest when compared with sepsis-associated laminitis. Objective: To characterize digital lamellar inflammation in horses in a euglycemic-hyperinsulinemic clamp (EHC) model of laminitis. Methods: Sixteen healthy adult Standardbred horses. Methods: Prospective experimental study. Horses underwent EHC or saline infusion (CON) for 48 hours or until the onset of Obel grade 1 laminitis. Horses were euthanized, and digital lamellar tissue was collecte...
The effect of age on foal monocyte-derived dendritic cell (MoDC) maturation and function after exposure to killed bacteria. Neonatal foals are uniquely susceptible to certain infections early in life. Dendritic cells (DC) are vital in the transition between the innate and adaptive immune response to infection, but DC biology in foals is not fully characterized. Monocyte-derived DC represent a suitable in vitro model similar to DC that differentiate from monocytes recruited from circulation. We hypothesized that foal monocyte-derived DC (MoDC) would exhibit age-dependent phenotypic and functional differences compared to adult horse MoDC. MoDC generated from 9 horses (collected once) and from 8 foals (collected at 1,...
The Effect of Autologous Protein Solution on the Inflammatory Cascade in Stimulated Equine Chondrocytes. Cartilage injury occurs commonly in equine athletes, often precipitating posttraumatic osteoarthritis (PTOA). Orthobiologics such as autologous conditioned serum (ACS) and autologous protein solution (APS) may be useful in decreasing posttraumatic inflammation, thereby preventing PTOA. The objective of this study was to quantify cytokine concentrations in ACS and APS and evaluate the protective effects of ACS and APS on inflamed chondrocytes cultured . We hypothesized that the combination of platelet-derived growth factors (PDGF) and anti-inflammatory cytokines present in APS would be superior...
