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.
Equine autologous platelet concentrate is a leukocyte-rich platelet-rich plasma with a high interleukin-1Ra-to-interleukin-1β ratio and high transforming growth factor-β1 concentration. To quantify platelets, leukocytes, cytokines, and growth factors in ProVet autologous platelet concentrate (APC). We hypothesized that APC would contain significantly increased leukocytes and platelets compared to whole blood and significantly increased concentrations of anti-inflammatory cytokines and growth factors compared to serum. Unassigned: Blood was obtained from 6 horses and processed to produce APC. Leukocyte and platelet concentrations were quantified in whole blood and APC. Cytokines, including interleukin (IL)-1β, IL-4, IL-6, IL-10, tumor necrosis factor-α, and IL-1Ra, and growt...
Analysis of lipid mediator profiles in the blood of horses with equine asthma using UPLC-MS/MS. Equine asthma (EA) is a chronic inflammatory disease of the lower respiratory tract in horses, which is mainly triggered by dusty hay. EA is becoming increasingly acknowledged as a valuable animal model for studying human asthma. Research on the pathogenesis of EA has primarily focused on the associated cells and cytokines involved. However, the role of inflammation-related lipid mediators (LM) in the development and progression of equine asthma remains elusive. LMs are categorized into pro-inflammatory arachidonic acid (AA)-derived leukotrienes (LTs) and prostaglandins (PGs), as well as infla...
How Inflamed Is the Horse in Training? Insights into Exercise-Induced Acute Phase Response in Endurance Horses. The article aimed to review the current literature analysing the complexity of an exercise-induced acute phase response in athletic horses undergoing intense training and endurance competitions. Since the endurance discipline demands physical fitness, exceptional health and excellent adaptation to an increasing workload, diagnostic methods of assessing the factors mentioned above are highly required. Athletic horses in endurance training undergo numerous metabolic but also immune adaptations, including changes in pro-inflammatory and anti-inflammatory cytokine levels. The inflammatory reaction...
Horse immune response of recombinant Lawsonia intracellularis vaccine: Assessing the immunomodulatory impact of probiotic supplementation. Equine proliferative enteropathy (EPE), caused by Lawsonia intracellularis induces intestinal epithelial hyperplasia, resulting in malabsorption, weight loss, colic, and diarrhea. Despite its clinical and economic importance, no equine-specific vaccine is commercially available. Recombinant subunit vaccines are a safe and scalable alternative; however, their immunogenicity often requires improvement. Probiotic supplementation with Bacillus toyonensis may act as an immunomodulatory strategy to potentiate vaccine efficacy. This study aimed to evaluate the immunogenicity of a recombinant protein ...
An in-hospital clinical trial assessing nebulized lidocaine compared to saline for treatment of asthma in horses. Corticosteroids are the main pharmacologic treatment for equine asthma (EA) but may have adverse effects in metabolically unstable horses. Recent pilot studies support the use of nebulized lidocaine as an alternative treatment option. Objective: Nebulized lidocaine will improve EA-associated clinical variables and airway inflammation. Methods: Twenty client-owned horses diagnosed with EA. Methods: Randomized, blinded, in-hospital study comparing 1 mg/kg preservative-free 4% lidocaine (n = 10) nebulized via Flexineb (twice daily for 7 doses) to 0.9% saline control (n = 10). Clinical examin...
Interleukin-4 changes the transcriptome, ECM-associated components and function of mare endometrial fibroblast: Insights from healthy and fibrotic cells. Fibrosis remains incompletely understood, particularly in terms of how immune mediators shape stromal programs. We used a spontaneous large‑animal model-endometrosis (equine endometrial fibrosis) to define how interleukin‑4 (IL‑4) reprograms fibroblasts from healthy and fibrotic endometrium. Primary fibroblasts were exposed to IL‑4 (10 ng/mL) for 48 or 96 h. At 48 h, bulk transcriptomes revealed 1307 differentially expressed genes (DEGs; 648 up, 659 down) and 1271 DEGs (645 up, 626 down) in fibroblasts derived from endometria without or with endometrosis, respectively. Enrichment an...
TGF-β1 and estradiol modulate prostaglandin concentrations and related gene expression in equine endometrium during the follicular phase. Transforming growth factor (TGF)-β1 is a pro-fibrotic cytokine that affects extracellular matrix (ECM) deposition and fibroblast activity. 17β-Estradiol (E), the dominant ovarian steroid during the follicular phase (FLP) of the estrous cycle, can also influence ECM remodeling and fibrosis, through prostaglandin (PG) synthesis. PGs have opposing roles in fibrosis, with PGE₂ showing anti-fibrotic effects and PGF₂α promoting fibrosis. Equine endometrosis, whose main pathological feature is fibrosis, is marked by chronic inflammation and ECM accumulation, and may involve mediators like TGF-...
A novel oral immunotherapy strategy using transgenic barley induces Culicoides allergen-specific immune responses in horses. Insect bite hypersensitivity (IBH) is a seasonal, IgE-mediated allergic dermatitis of horses caused by salivary gland proteins of biting midges ( spp.). Current management relies on relief of clinical signs and on physical protection. In a previous pilot study, healthy horses were fed transgenic barley expressing a allergen via a special spiral bit, which successfully induced allergen-specific antibody responses. Building on this concept, the present study aimed to evaluate a more practical feeding approach, delivering transgenic barley expressing the major allergen Cul o 2p in a feed-compat...
RNA-seq evaluation of equine alveolar macrophages and monocyte-derived macrophages exposed to an inflammatory stimulus (short communication). Macrophage populations in the lung, including resident alveolar macrophages (AMs) and recruited monocyte-derived macrophages (MDMs), recognize the inhaled particulates in barn dust that cause severe equine asthma and orchestrate an immune response though the cytokines they produce. Despite their importance, the specific contributions of these macrophage subsets to lower airway inflammation remain poorly understood. This exploratory in vitro study investigated the likely contributions of AMs and MDMs from healthy horses to the early inflammatory response using RNA-seq. If biologically importan...
Activation of the S100A8/A9 Alarmin Amplifies Inflammatory Pathways in Equine Ascending Placentitis. Ascending placentitis is a significant cause of equine pregnancy loss, yet the upstream inflammatory triggers are poorly defined. Recently, we identified S100A8/S100A9 (S100A8/A9) alarmins as potential upstream regulators in a chronic equine placentitis model. The current study aimed to determine whether this upregulation is sustained in the acute model and in clinical cases, and to elucidate the expression of their downstream inflammatory mediators. Using an experimental model, we quantified mRNA expression in acute ( = 5) and chronic ( = 6) placentitis induced by ssp. . We found mRNA expre...
Functional and biochemical inflammatory responses to low-dose intra-articular recombinant equine IL-1β: a pilot study. Low-dose intra-articular injection of recombinant equine interleukin-1β (reIL-1β) may offer a useful model for studying early onset or subclinical joint inflammation in horses. This pilot study aimed to determine the lowest intra-articular dose of reIL-1β required to produce biochemical evidence of synovitis, and to correlate synovitis biomarkers with functional, upper-body asymmetry parameters. Saline (control) and 50, and 75 ng reIL-1β were injected into the left or right intercarpal joint of three ( = 3) horses in a three-way crossover design. Synovial fluid was collected by aseptic art...
Characterization and priming of equine muscle-derived mesenchymal stem cells to enhance their anti-inflammatory and immunomodulatory profiles. A minimally invasive microbiopsy-based method for the isolation of mesenchymal stem cells (MSCs) from equine skeletal muscle (M-MSCs) provides a readily accessible source of MSCs for clinical applications. We examined the expression of genes associated with immunomodulation and anti-inflammatory pathways, in addition to those of growth factors and the major histocompatibility complex (MHC) molecules I and II, at constitutive levels and after priming with inflammatory cytokines, an immunostimulant, and heat-shocking. While there was notable variation between the M-MSCs from each of the horses i...
Impact of melatonin on inflammatory cytokine profiles in 24-hour cultured equine uterine explants’. Melatonin has demonstrated beneficial effects in regulating inflammatory processes in various tissues, but its role in mare uterine physiology remains unclear. Objective: To investigate the effects of melatonin on the gene expression of cytokines (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in equine uterine explants cultured for 6, 12, or 24 hours. Methods: The study was divided into two experiments. Part 1 aimed to evaluate the cytotoxicity of melatonin at concentrations of 0, 0.5, 1, 2, 4, and 8 mM on endometrial cells. Part 2 aimed to determine the expression of inflammatory cytokines in uterin...
Limited impacts of dietary Protandim Nrf2 Synergizer on antioxidant and inflammatory status of mature, sedentary horses. Reactive oxygen species are normal by-products of cellular metabolism but may have detrimental effects on cellular matrices and excite inflammatory pathways when overproduced. To test the hypothesis that supplementation of an herbal extract combination would: 1) improve antioxidant status; 2) increase anti-inflammatory cytokines; and 3) decrease pro-inflammatory cytokines, 40 mature, sedentary stock-type horses (32 mares, 8 geldings, mean±SD; 15.7 ± 4.9 yr, 519 ± 46 kg) were stratified by age, sex, and body weight and randomly assigned to one of four dietary treatment groups for 5...
Equine monocyte-derived macrophages revisited: isolation and comprehensive characterization of pro- versus anti-inflammatory polarisation. Macrophages play key roles in tissue homeostasis and regeneration-associated inflammation. Unlike humans, a reliable protocol to obtain and polarise equine monocyte-derived macrophages is lacking. In this study the polarisation of equine macrophages, derived from CD172a peripheral blood monocytes is described. After differentiation, IFN-γ/LPS or IL-4 were used to induce pro- and anti-inflammatory phenotypes, respectively. Evaluation criteria included morphology, mRNA (RT-qPCR) and protein expression (flow cytometry, immunofluorescence), nitric oxide and arginase production, cytokine secretion...
Monitoring Weaning Stress in Fillies and Colts on a Thoroughbred Breeding Farm by Cortisol and Blood Inflammatory Markers: The Benefits of Gradual Separation and Social Support. Weaning represents a major developmental milestone for foals, especially when 4- to 7-month-old foals are abruptly separated from their dams. Studies have shown that the post-weaning period is associated with physiological and psychological stress, which may affect immune function. The present study aimed to describe and analyze the pattern of blood inflammatory biomarkers related to the innate immune system. A gradual foal-dam separation procedure was chosen, which included post-weaning social buffering by a familiar adult horse. Twelve Thoroughbred foals (six fillies, six colts) aged 4-6 mon...
Hippobosca equina: Influences on oxidative stress and immune-regulating cytokine responses in horses. Hippobosca equina, a common ectoparasite of horses, poses a significant challenge to equine health worldwide. This study provides a molecular characterization of H. equina and examines its impact on host immune responses and oxidative stress. Genetic analysis of samples from various regions revealed notable homogeneity, indicating limited genetic variation among populations. Phylogenetic analysis demonstrated close genetic relationships among sequences from Egypt, France, Kazakhstan and Portugal, while also showing comparable but more distant identities to sequences from China, Denmark, Finlan...
The Role of Short-Chain Fatty Acids (SCFAs) in Colic and Anti-Inflammatory Pathways in Horses. Equine colic remains a prevalent and potentially life-threatening condition with multifactorial origins, including dietary imbalances, stress, and microbial dysbiosis. Central to equine gut health is the production of short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, generated through microbial fermentation of dietary fibers in the hindgut. These metabolites not only serve as vital energy sources but also play crucial roles in maintaining intestinal barrier integrity, modulating motility, and suppressing inflammation. This review explores the role of SCFAs in equine...
Synovial chemokine and cytokine profiles in horses with and without systemic Borrelia burgdorferi infection. Lyme arthritis, a well-documented subtype of arthritis in humans and dogs, is caused by Borrelia burgdorferi and spread primarily through ticks (Ixodes spp.). While Lyme disease in horses is known to cause a variety of clinical signs, its involvement in the development of equine arthritis is controversial. As climate change enables tick populations to expand, more horses could be exposed to B. burgdorferi; therefore, a greater understanding of how Lyme disease affects joints is critical to preserving soundness. Objective: To determine if systemic, naturally occurring Lyme disease had a discern...
Towards understanding mare endometrosis: ex vivo study on the role of relaxin. Mare endometrosis remains a poorly understood pathological process. Objective: Mare endometrial tissue with endometrosis was used to determine the effects of relaxin (RLX). Healthy tissues that were left untreated (H), or treated with vehicle (Hveh), and tissues with endometrosis that were left untreated (E), treated with vehicle (Eveh), and treated with RLX (10, 25, 50 nM; ER) were used for an ex vivo system for 72 h. Methods: Tissue histological examination, and immunoenzymatic measurement of the concentrations of transforming growth factor β (TGF-β), interleukins (IL-6 and IL-8), and pr...
Uterine proteomic and cytokine profiling show that Streptococcus equi subsp. zooepidemicus induces immune-metabolic dysregulation and may predispose mares to endometrosis. This study aims to characterize and compare the uterine fluid proteome and cytokine profile of reproductively healthy mares (HM; n = 15) and mares with Streptococcus equi subsp. zooepidemicus (S. zooepidemicus)-associated endometritis (SAE; n = 9). Uterine flush samples collected during the follicular phase were analyzed by shotgun proteomics and multiplex cytokine assays. Equine proteins were mapped to human orthologs, and enrichment and network analyses were performed using g:Profiler, Metascape, ToppGene, and STRING/MCODE. SAE mares showed higher levels of IL-1α, IL-1β, GRO, IL12p...
Transcriptomic Insights into Tumor Necrosis Factor α’s Role in the Fibrosis-Related Processes of Equine Endometrial Fibroblasts. Equine endometrosis is a chronic degenerative condition of the endometrium. A hallmark feature of endometrosis is endometrial fibrosis accompanied by degenerative changes in the adjacent tissue structure. Tumor necrosis factor α (TNFα), a pleiotropic cytokine produced by various immune cells, plays a dual role in coordinating immune responses and regulating cell/tissue homeostasis, making it an important regulator of fibrotic-related disorders. However, the exact role of TNFα in the development of equine endometrial fibrosis remains to be discovered and explained. Therefore, the main aim of...
The Concentration and Duration of Lipopolysaccharide Stimulation Produce Different Cytokine Responses in an Ex Vivo Whole Blood Model in Horses. Lipopolysaccharide (LPS) is frequently used in equine research to model clinical endotoxemia; however, there is no standardized protocol for inducing cytokine production in equine whole blood. To address this knowledge gap, the goal of this study was to compare the cytokine responses elicited by three different LPS stimulation protocols. Whole blood was collected from six healthy horses (aged 5-30 years; mixed breeds and genders) from the North Carolina State University teaching herd (IACUC #23-412). Sixty milliliters of heparinized blood were aseptically drawn and divided into 15 mL aliquots....
Inhibition of interleukin-1 receptor-associated kinase (IRAK)-4 provides partial rescue of interleukin-1 beta induced functional and gene expression changes in equine tenocytes. Interleukin 1 beta (IL-1β) is upregulated following a tendon injury and in vitro studies have shown that it leads to numerous negative effects on tendon cell function and gene expression. IL-1β activates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and we hypothesised that inhibiting NF-κB activation would mediate the negative effects of IL-1β on equine tendon cells in 3-dimensional (3D) cultures. Results: Here, we tested three inhibitors of NF-κB signalling (Bortezomib, BAY11-7082 and Wedelolactone) along withTJ-M2010-5, an inhibitor of MyD88, which is a critic...
Impact of IL-6 and TGF-β1 on equine mesenchymal stromal cell homing gene expression. Mesenchymal stromal cells (MSCs) support wound healing through immunomodulation and by promoting tissue organization. Cell tracking studies demonstrate that MSCs must 'home' to injuries in order to participate in reparative processes. It has been reported that in vivo cell tracking labels, including superparamagnetic iron oxide particles (SPIOs), can alter MSC homing. Homing is thought to occur in coordinated steps including tethering, activation, arrest, diapedesis, and migration, guided by chemotactic stimuli. Equine distal limb injuries, which are commonly treated with MSCs, possess a disti...
Does the Relationship Between Microelements (Copper, Zinc and Selenium) and Proinflammatory Proteins (IL-6, IL-8 and Tissue Factor) Have Diagnostic Value in Equine Medicine? Some correlations between serum Cu, Zn and Se and cytokines have been reported in humans. Especially, the Cu:Zn ratio corresponded with inflammation. To date, relationships between microelements and proinflammatory proteins are poorly understood in horses. The aim of the study was to evaluate whether Cu, Zn and Se may influence turnover of IL-6, IL-8 and tissue factor (TF) in breeding and working horses. Blood samples obtained from 66 horses were analysed. There were 37 pregnant broodmares of different breeds, 13 barren broodmares and 16 race Thoroughbred horses. Serum Cu, Zn and Se concentrat...
Revitalizing equine metabolism: how SHBG improves mitochondrial function and reduces inflammation. Equine metabolic syndrome (EMS) is associated with chronic low-grade inflammation, disruptions in mitochondrial dynamics and function, and an increased risk of developing laminitis. Recent research has highlighted that reduced levels of sex hormone-binding globulin (SHBG) in the bloodstream are linked to higher susceptibility to obesity, insulin resistance, and diabetes, potentially contributing to broader metabolic imbalances. This study aimed to evaluate whether exogenously administered SHBG could protect adipose-derived stem cells from horses affected by EMS (EqASC) against mitochondrial dy...
Th1 and Th2 cells in equine endometrosis and their interactions with endometrial fibroblasts. Mare endometrosis is a chronic degenerative condition of the endometrium, primarily characterized by fibrosis, involving interactions among fibroblasts, immune cells, and epithelial cells regulated by cytokines and growth factors. T helper (Th)1 and Th2 cells seem to play a pivotal role in fibrosis. However, their roles in equine endometrial fibrosis remain unknown. This study explores Th1 and Th2 cell distribution across different stages of endometrium histopathological Kenney and Doig categories; and evaluated their secretome effects on non-fibrotic endometrium derived fibroblast functional ...
Abnormal Fetuin-A levels in obese horses are associated with activated TLR4/NF-ƙB/MAPK axis and depleted FBXW7 E3 ubiquitin ligase. Fetuin-A (FetA) is a multifactorial glycoprotein primarily synthesized by the liver with additional expression in adipose tissue, the abundance of which is tightly regulated by the FBXW7 E3 ubiquitin ligase. Recently, FetA has been implicated in the pathogenesis of insulin resistance and associated metabolic failures in humans through its potent and selective inhibition of insulin receptor tyrosine kinase activity, however, no studies have yet directly investigated its role in the development and progression of equine obesity. In this investigation, FetA levels were measured in serum, liver, a...
Interleukin 17A in the fibrotic-related processes in endometrosis in the mare. Equine endometrosis is a chronic degenerative condition with fibrosis being one of the most significant characteristics. A growing body of evidence indicates the critical role of interleukin (IL)-17 in fibrotic disorders. However, its exact role during equine endometrosis remains to be discovered and explained. The main aim of the current study was to establish the expression of IL-17A signaling components in equine endometria with and without endometrosis as well as the effects of IL-17A on the transcriptomic signature, cellular functional characteristics, expression of extracellular matrix (...