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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.
Genomics in Equine MEED: Whole-Genome Sequencing and Target Mutation Identification. Multisystemic eosinophilic epitheliotropic disease (MEED) is a rare and severe equine disorder characterized by chronic eosinophilic inflammation, epithelial disruption, and multi-organ involvement, with an undefined genetic basis. We performed the high-depth (~40×) whole-genome sequencing of an affected horse and compared it to 40 control genomes. Over 6.3 million variants were identified, with moderate- and high-impact variants enriched in low-frequency categories, including rare and private variants absent from the controls. The affected horse was dominated by missense mutations, with rela...
Immunohistological characterization of equine synovial tissue in metacarpophalangeal joints of different ages and osteoarthritis status. Synovial macrophages' role in equine osteoarthritis (OA) is not well understood, despite horses being a model for human degenerative joint disorders. Equine synovial macrophages' characterization is limited and age-related changes are not described. This study aimed to evaluate surface marker distribution and expression from potential synovial tissue macrophages in foals, adult non-affected, and OA-affected horses. Unassigned: Surface markers (CD14, CD16, CD206) were quantitatively evaluated on dorsal villous synovial biopsies from the metacarpophalangeal joint of foals (F), non-affected (cont...
Dexmedetomidine infusions improve cardiovascular and renal function in anaesthetised, experimentally endotoxaemic horses. Dexmedetomidine infusions are beneficial in anaesthetised endotoxaemic horses when administered concurrent to endotoxin, but post-conditioning effects are unknown. Objective: To evaluate whether a dexmedetomidine infusion is beneficial in horses administered Escherichia coli O55:B5 lipopolysaccharides (LPS) endotoxin prior to anaesthesia. Methods: Randomised controlled in vivo experiment. Methods: Ten systemically healthy horses were instrumented for acquisition of cardiac index (CI) using thermodilution. Horses received IV LPS (0.1 μg/kg bwt) immediately prior to anesthesia. Horses receive...
Influence of Housing and Fecal Egg Count on Cytokine Profiles (IL-4 and IL-13) in Equines. Strongyles are parasitic roundworms that cause significant gastrointestinal infections in equines, primarily through contact with infected soil. Worldwide, strongylosis affects nearly 90% of horse populations. Objective: The objectives of our study were to determine if there was a relationship between fecal egg count (FEC) and housing types on interleukin IL-4 and IL-13. Methods: Horses (N=25) were separated into two groups based on housing conditions: pasture (housed on pasture 24/7; PS, N=13) and semi-intensive (housed in stalls with turnout overnight; SI, N=12). Within each housing group, t...
Allogeneic Platelet-Rich Gel Supernatant Reprograms the Cytokine and Growth Factor Microenvironment in an Equine In Vitro Inflammatory Tendon System. Tendinopathy involves a dysregulated inflammatory microenvironment in which cytokines, growth factors (GF) and extracellular matrix components interact dynamically. Platelet-rich plasma (PRP) is widely used as a regenerative therapy, but its mechanisms of action in inflamed tendon remain unclear. This study evaluated whether platelet-rich gel supernatant (PRGS) reprograms the inflammatory-anabolic mediator network in an equine in vitro tendon explant system stimulated with lipopolysaccharide (LPS). Tendon explants were cultured under six experimental conditions, including non-stimulated contro...
Circulating microRNA profiles as diagnostic and prognostic biomarkers for acute and carrier Theileria equi infection. Equine piroplasmosis caused by Theileria equi exhibits a wide clinical spectrum ranging from acute disease to lifelong asymptomatic carriage, posing significant diagnostic and epidemiological challenges. In this cross-sectional case-control study, equines were classified as acutely infected, asymptomatic carriers, or uninfected controls based on clinical examination and quantitative PCR. Hematological and biochemical alterations were assessed, and plasma miRNA profiles were characterized using small RNA sequencing, followed by qRT-PCR validation of selected miRNAs. Cytokine gene expression in ...
Interleukins decrease epithelial protein and gene expression by K14 + CD105+ equine hoof progenitor cells. Progenitor cell epithelial to mesenchymal transition (EMT) could impact healing in the epidermal-dermal junction of the equine hoof stratum internum (SI). The hypothesis of this study was that K14 + CD105+ equine hoof SI progenitor cells assume a mesenchymal phenotype in the presence of inflammatory interleukins in vitro. Methods: K14 + CD105+ progenitor cell percentages isolated from proliferative scarred (fibrous) and healthy SI were quantified. Decellularized matrix was prepared from and K14 + CD105+ cells localized in healthy SI. Gene expression (CD44, CD105, E-cadherin, N-cadh...
In Vitro Characterization of an Equinized Anti-PD-L1 Antibody for Cancer Immunotherapy in Horses. Horses develop spontaneous tumors, typically in old age. Although local tumor control can be achieved using conventional therapies, systemic therapies are required to treat recurrent and/or metastatic tumors. Immune checkpoint inhibitors, such as anti-PD-L1 antibodies, have been approved for the treatment of various tumor types in humans; however, little is known about the immunosuppressive roles of the PD-1/PD-L1 pathway in horses, and the therapeutic potential of these inhibitors remains to be elucidated. Previously, we reported that the rat monoclonal anti-PD-L1 antibody 6C11-3A11 cross-rea...
Synthetic progestin treatment alters cytokine expression and impairs vaccine response in horses. Altrenogest is commonly used in equine veterinary medicine for the control of estrus, behavioral modifications, and maintenance of pregnancy. Recent studies have found that altrenogest may impact aspects of the immune system, including altering cytokine production in circulation and within the reproductive tract. Therefore, we hypothesize that this alteration may lead to a deviated immune response to vaccination. Sixteen mares were divided into two groups, with ten mares (n = 10) receiving long-acting injectable altrenogest (100 mg/mL; IM) administered every 10 days, and six mares (n =...
Serum-free medium modulates the immunomodulatory and anabolic function of equine bone marrow-derived mesenchymal stromal cells. Adult bone marrow-derived mesenchymal stromal cells (BM-MSCs) hold significant therapeutic potential in human and veterinary medicine. Traditionally, BM-MSC cultures use fetal bovine serum (FBS) to promote growth, but this practice introduces batch variability and xenogeneic contamination that complicate clinical translation. While serum-free medium (SFM) alternatives have been optimized for human MSCs, limited options have been explored for alternative or veterinary species. Here, we compared a chemically defined, customizable SFM formulation with conventional serum-containing medium (SCM) fo...
Intra-articular hydrogel therapeutics exhibit anti-inflammatory effects on cytokine-stimulated equine cartilage and synovial membrane explants. To investigate whether IA hydrogel therapeutics alter the inflammatory and/or degradative responses of articular cartilage (AC) and synovial membrane (SM) to cytokine stimulation. Unassigned: AC and SM tissue explants were stimulated with interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α) and simultaneously treated with triamcinolone acetonide, hyaluronic acid, collagen-elastin hydrogel microparticles (CEHM), or 2.5% polyacrylamide hydrogel (2.5% iPAAG) at 3 doses. Synovial membrane (n = 9 explants, 3 horses) was stimulated/treated for 18 hours, whereas AC (12 explants, 6 horses) wa...
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...
Extracorporeal shock wave therapy in equine and canine practice. To describe the proposed mechanism of action of shock wave therapy and discuss treatment considerations and guidelines for use in equine and canine practice. Unassigned: Client-owned animals with owner consent. Unassigned: Shock wave therapy is proposed to stimulate healing by generating forces that cause cells to undergo microtrauma and release anti-inflammatory cytokines and growth factors into the treated tissues. While the 4 types of shock wave therapies are discussed, electrohydraulic and piezoelectric are described in detail, as they are most utilized in veterinary medicine for the treat...
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...
Targeting Toll-like Receptor 2: synthetic diacylated lipopeptides polarize equine macrophages towards a pro-inflammatory phenotype. Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs), that play critical roles in initiating host immune defenses. TLR-2 agonists can activate innate immune cells and thus are attracting increasing attention as prophylactic and/or therapeutic agents against infectious diseases or in cancer immunotherapy. In this work, the impact of three synthetic diacylated lipopeptides (Mag-Pam2Cys_P48, MagPam2Cys_P80, and Mag-Pam2Cys_MAG1000) on equine monocyte-derived macrophages (moMΦ) phenotype and functionality was thoroughly investigated. MoMΦ were generated from circulatin...
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...
Postbiotics: Multifunctional Microbial Products Transforming Animal Health and Performance. Postbiotics, which are preparations of inanimate microorganisms and their components, have emerged as a promising functional ingredient in animal health and nutrition. Postbiotics are primarily composed of microbial cell fractions, metabolites, enzymes, vitamins, polysaccharides, and short-chain fatty acids. Unlike probiotics, postbiotics do not contain live microorganisms, which strengthens their greater stability and safety in feed/food formulations. Postbiotics offer several beneficial effects, including antioxidant, anti-inflammatory, immune-modulatory, and antimicrobial actions. They enha...
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...
