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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.
Evaluating ex vivo toll-like receptor agonist response as a potential biomarker in equine gastric ulcer syndrome. Equine gastric ulcer syndrome (EGUS) is highly prevalent in horses. Despite its presumed painful nature, evaluation of objective biomarkers associated with EGUS presence and severity remains limited. The objective of this study was to investigate the potential of interleukin-1 beta (IL-1β) release by peripheral blood mononuclear cells (PBMCs) following ex vivo stimulation of toll-like receptors 2 and 4 (TLR2 and TLR4) as a potential biomarker for EGUS status, with gastric lesions used as a proxy for presumed EGUS-associated pain. Venous blood was collected from 77 horses, PBMCs were isolated ...
Alpha-2-Macroglobulin-Enriched Plasma Modulates Inflammatory and Proteolytic Pathways in Experimental Equine Musculoskeletal Models. Joint inflammation and extracellular matrix degradation are major contributors to the development of equine osteoarthritis and reduced athletic performance. Alpha-2-macroglobulin is a naturally occurring broad-spectrum inhibitor of proteases and inflammatory mediators that has emerged as a promising orthobiologic therapy. This study investigated the anti-inflammatory and matrix-protective effects of alpha-2-macroglobulin-enriched plasma in complementary in vitro and ex vivo equine models. Primary equine chondrocytes and synoviocytes isolated from healthy horses were stimulated with interleukin...
Evaluation of a commercial multiplex immunoassay for assessing uterine inflammation in mares susceptible to persistent breeding-induced endometritis. Persistent breeding-induced endometritis (PBIE) is characterized by a prolonged and dysregulated uterine inflammatory response following breeding. Although inflammatory cytokines are central to the post-breeding immune response, their assessment in the equine uterus has historically relied largely on gene expression analyses. Multiplex immunoassays provide an opportunity to simultaneously quantify multiple cytokine proteins within uterine secretions; however, the application of equine-specific multiplex immunoassays utilizing the Luminex platform to low-volume uterine lavage (LVL) fluid remain...
Effects of omeprazole therapy administered via different routes on urinary parameters and selected interleukins in horses with equine gastric ulcer syndrome. Equine gastric ulcer syndrome (EGUS) is commonly treated with proton pump inhibitors such as omeprazole, administered orally or by injection. In humans, omeprazole has been associated with acute interstitial nephritis (AIN) and acute kidney injury (AKI), potentially linked to oxidative stress, and urinary interleukins may serve as early non-invasive markers. However, this association has not been established in horses. Objective: To evaluate the effects of oral and injectable omeprazole on basic urinary parameters and selected interleukin levels, with particular emphasis on the potential risk ...
Use of extracorporeal hemoperfusion in a 2-day-old foal with neonatal sepsis. A 2-day-old Miniature Horse filly presented with severe clinical and clinicopathologic findings consistent with neonatal sepsis, failure of transfer of passive immunity, and aspiration pneumonia. The filly initially was treated with broad spectrum antimicrobials, hemodynamic support, and hyperimmune plasma. Because of a lack of improvement within the first 24 h, extracorporeal blood purification and cytokine removal were implemented. The foal underwent hemoperfusion (HP) using a polymer-based device (VetResQ). Reported notable changes during and after treatment included improved physical exam...
Differential Serum Cytokine Profiles in Aborting and Subclinically Infected Pregnant Mares with Equine Herpesvirus Type 1. Equine herpesvirus type 1 (EHV-1) is a major cause of reproductive loss in mares. This cross-sectional field study evaluated serum concentrations of interleukin-2 (IL-2), interleukin-10 (IL-10), interferon-alpha (IFN-α), and interferon-gamma (IFN-γ), together with the IL-10/IL-2 and IFN-γ/IL-10 ratios, in 26 vaccinated pregnant Thoroughbred mares. The analytical cohort comprised healthy, EHV-1 PCR-negative mares (HM, n = 10), EHV-1 PCR-positive mares sampled within 4 h after fetal expulsion at approximately the sixth month of gestation (AM, n = 9), and EHV-1 PCR-positive pregnant mares with...
Cord blood mesenchymal stromal cells combined with hyaluronic acid show symptom-modifying and potential disease-modifying effects in an equine osteoarthritis fetlock chip model. Osteoarthritis (OA) is a major cause of lameness in horses, and current therapies largely address clinical signs rather than disease progression. Mesenchymal stromal cells (MSCs) have shown promise as disease-modifying biologics, but their effects on joint structure and immunologic phenotype remain incompletely characterized. Unassigned: To evaluate the safety and efficacy of pooled cryopreserved equine umbilical cord blood-derived MSCs (eCB-MSCs) combined with hyaluronic acid (HA) for surgically induced fetlock OA in horses, using integrated clinical, imaging, and synovial biomarker outcomes....
Neosaxitoxin Downregulates Inflammation in an Equine In Vivo Model of Osteoarthritis. Chronic synovial inflammation is a hallmark of osteoarthritis progression and is tightly regulated by synovial macrophages. Recently, voltage-gated sodium channels (NaV) have emerged as potent modulators of macrophage-driven inflammation, positioning them as novel therapeutic targets. Among selective NaV channel blockers, neosaxitoxin exerts remarkable anesthetic and immunomodulatory effects; however, its effects on joint inflammation upon intra-articular delivery remain unexplored. Using an equine model of bilateral carpal osteoarthritis, this study evaluated the immunomodulatory and tissue-p...
Short-term effects of pulsed electromagnetic field therapy on subjective flexion-associated lameness responses and circulating cytokines in horses with distal tarsal osteoarthritis. Pulsed electromagnetic field (PEMF) therapy is commonly used in equine sports medicine for its proposed anti-inflammatory effects; however, limited controlled studies have evaluated its physiologic effects in horses. Objective: The objective of this study was to investigate the effects of PEMF therapy on flexion-induced lameness and circulating cytokines in horses with radiographic evidence of distal tarsal osteoarthritis. Methods: Six mares were enrolled in a repeated-measures crossover design in which each horse served as its own control. Horses were evaluated at baseline (sham PEMF) and at ...
Oxidative Stress and Inflammatory Responses in Horses Naturally Infected with Theileria equi. Equine piroplasmosis, caused by the intraerythrocytic protozoan , is a globally distributed tick-borne disease characterized by persistent infection and variable clinical manifestations. Although oxidative stress has been implicated in the pathogenesis of several hemoprotozoan diseases, information regarding redox imbalance and its relationship with inflammatory responses in horses naturally infected with remains limited. This study aimed to evaluate oxidative stress, antioxidant status, inflammatory cytokines, and clinicopathological alterations in horses naturally infected with . Thirty-fiv...
The in vitro application of high-intensity laser therapy on equine platelet-rich plasma and autologous protein solution does not alter select cytokine and growth factor concentrations. To quantify the effects of high-intensity laser therapy (HILT) on the concentration of key immunomodulatory cytokines and growth factors in equine platelet-rich plasma (PRP) and autologous protein solution (APS). We hypothesized that HILT treatment of PRP and APS in vitro would increase the concentration of cytokines and growth factors compared to untreated controls. Unassigned: Whole blood was collected from 6 adult horses housed at the University of Pennsylvania in March 2025 and processed into PRP or APS using commercially available systems (Zoetis). Platelet-rich plasma and APS samples wer...
Systematic establishment of approaches to the detection of equine macrophage polarization and their application in pathogenic infection. Macrophage phenotypic adaptation critically regulates inflammatory balance during infection; however, progress in equine immunology has been limited by a lack of specific tools for standardized identification. To address this gap, we established a reliable, antibody-based detection method for characterizing equine macrophage M1-like and M2-like marker profiles. After initially validating canonical marker genes via qPCR, we developed specific monoclonal antibodies targeting the differentially expressed surface proteins CD80 (M1-like) and CD163 (M2-like). These novel antibodies enabled the creat...
Anti-Inflammatory and Metabolic Effects of Fresh Versus Freeze-Dried Platelet-Rich Plasma on Equine Osteoarthritis in an Ex Vivo Cartilage-Synovium Explant Co-Culture System: A Pilot Study. Equine osteoarthritis (OA) is a major cause of lameness and economic loss in horses. While platelet-rich plasma (PRP) has clinical potential, the biological effects of fresh PRP (F-PRP) and freeze-dried PRP (FD-PRP) remain insufficiently defined. This pilot study compared 25% and 50% F-PRP and FD-PRP in an interleukin-1β-induced equine cartilage-synovium explant co-culture model. PRP treatments reduced inflammatory responses, with significant downregulation of COX-2 and PGE2 expression, and 25% F-PRP showed the most consistent inhibition of nitric oxide production. PRP also significantly redu...
Sixty minutes of daily solitary turnout improved physiological and behavioral indicators of stress and welfare in stall-housed horses. Housing horses in stalls restricts natural roaming behaviors, which in turn increases stress and stereotypic behaviors. Daily turnout for voluntary exercise is common for stress mitigation, but there is no consensus for optimal duration of turnout sessions. Objective: We sought to understand how minimal and moderate-duration daily turnout affects behavioral and physiological stress indicators. Methods: In a Latin-square design, adult Quarter horses (N=11) were allowed 0, 15, or 60 minutes/day of solitary turnout for 12-day periods. In-stall behaviors and 24-hour time budgets were assessed on d...
Effects of Nebulized Alpha-2 Macroglobulin in Horses with Lower Airway Inflammation. Equine asthma is a chronic inflammatory airway disease with limited safe long-term treatments. Alpha-2-macroglobulin (A2M), a natural anti-inflammatory protease inhibitor, may provide a novel non-steroidal therapeutic option for horses with lower respiratory tract inflammation. Objective: To characterize the impact of nebulization with alpha-2-macroglobulin (A2M) on clinical signs, bronchoalveolar lavage cytology, and local and systemic cytokine response in horses with lower respiratory tract inflammation. Methods: Thirteen university-owned horses with lower airway inflammation were randomized...
Interleukin 12 on extracellular matrix-related factors and functional characteristics of equine endometrial fibroblasts. Tissue fibrosis is described as the excessive accumulation of extracellular matrix (ECM) components. This process is associated with inflammation, and the interaction between fibroblasts and immune cells plays a key role, driving the progression of fibrosis. Results of recent study suggest that interleukin (IL)-12 may play a role in the processes associated with the development of fibrosis. This proinflammatory cytokine is synthesized and released by macrophages, dendritic cells, and B cells. Objective: The objective of this study was to determine: (i) the expression of IL-12 and its receptor ...
Single-dose intravenous α2-agonists do not acutely alter anti-inflammatory bioactive protein profiles but reduce interleukin-8 in equine autologous protein solution and platelet-rich plasma. Determine the acute effects of xylazine and detomidine on concentrations of selected growth factors, cytokines, and α2-macroglobulin (A2M) in platelet-rich plasma (PRP) and autologous protein solution (APS) and the long-term effects of these sedatives on serum A2M. We hypothesized that sedative administration would decrease concentrations of all bioactive proteins in PRP and APS acutely and A2M in serum for 6 days following sedative administration. Unassigned: 6 horses were randomized to receive IV xylazine (200 mg) or detomidine (10 mg). Blood was collected before and 5 minutes after sedativ...
Pilot Study of an Alpha-2-Macroglobulin-Enriched Plasma-Derived Orthobiologic Preparation in Sport Horses with Chronic Degenerative Joint Disease. Chronic joint disease is a major cause of lameness and reduced performance in sport horses and is characterized by persistent synovial inflammation and protease-mediated matrix degradation. This exploratory prospective pilot study investigated clinical outcomes and synovial biomarker changes following intra-articular administration of an α-2-macroglobulin plasma-derived preparation. Twenty client-owned sport horses were observed in the treatment group (n = 10) or a comparison group (n = 10) and monitored for up to 180 days under field conditions. Clinical outcomes were assessed longitudinally...
Effect of N-acetyl cysteine treatment on uterine cytokine and chemokine profiles in mares with persistent breeding-induced endometritis. Persistent breeding-induced endometritis (PBIE) is a major cause of infertility in mares. Recent research has shown that PBIE-affected mares treated with intrauterine N-acetyl cysteine (NAC) 12 hours before breeding showed no improvement in clinical signs at 12- and 60-hours post-breeding. Objective: The present study was designed to examine the effects of NAC treatment on the uterine inflammatory cytokine and chemokine profiles in PBIE-affected mares. Methods: Using a randomized, blinded, cross-over design, mares susceptible to PBIE (n=9) were allocated to Control and Treatment cycles with at...
Combined PRP and CCP Therapy Suppresses Inflammation and Protects Cartilage in Post-Traumatic Osteoarthritis. This study aimed to evaluate the therapeutic effects of platelet-rich plasma (PRP) and Cervus and Cucumis polypeptide (CCP) injections in rats with post-traumatic osteoarthritis (OA). The model was established by transection of the anterior cruciate ligament, and the animals were subsequently treated with PRP and CCP. Articular cartilage degeneration was assessed through gross morphological observation, histopathological staining, and a standardized scoring system. Concurrently, pain-related behaviors, joint swelling, levels of inflammatory cytokines, and markers associated with extracellular ...
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. Background: 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-cadhe...
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...
