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Topic:Interleukins
Interleukins are a group of cytokines, which are signaling proteins, that are produced by various cells in the horse's body, including immune cells. They are involved in the regulation of immune responses, inflammation, and hematopoiesis. Interleukins facilitate communication between cells during immune responses and can influence the behavior of other cells. In horses, interleukins such as IL-1, IL-6, and IL-10 have been studied for their roles in inflammatory processes and immune regulation. Their expression and regulation are important for understanding immune function and disease pathogenesis in equine health. This page compiles peer-reviewed research studies and scholarly articles that explore the roles, mechanisms, and clinical implications of interleukins in horses.
Phenotypic Shift of an Inflammatory Eosinophil Subset into a Steady-State Resident Phenotype after 2 Years of Vaccination against IL-5 in Equine Insect Bite Hypersensitivity. Eosinophils play a key role in allergic diseases such as insect bite hypersensitivity (IBH). Together with Th2 cells, they shape the course of inflammation in associated type I/IVb allergies. Therefore, a virus-like particle (VLP)-based vaccine targeting equine interleukin-5 (eIL-5), eIL-5-CuMV-TT, was developed to interfere with the IL-5 dependency of eosinophils by inducing the production of anti-self-IL-5 antibodies and alleviating clinical signs in IBH-affected horses. A previous study highlighted the presence of two eosinophil subsets, steady-state resident eosinophils (rEos) and inflamma...
Oral probiotic administration attenuates postexercise inflammation in horses. Probiotics are commonly incorporated into equine diets to impart health and performance benefits; however, peer-reviewed evidence supporting their efficacy in horses is limited. Interestingly, bacteria from the Bacillus genus are gaining interest for their unique ability to impact metabolic, immune, and inflammatory pathways. The objective of this trial was to evaluate a selection of Bacilli for their role in altering the inflammatory response in horses to exercise. Eighteen horses were utilized in a randomized cross-over trial. Horses were randomly assigned to one of 6 starting treatments inc...
Monoclonal antibodies for equine IL-1β enable the quantification of mature IL-1β in horses. Interleukin-1β (IL-1β) is one of the key mediators of inflammation during innate immune responses. Mature bioactive IL-1β mediates essential host defense mechanisms but also has a mechanistic role in several autoinflammatory and degenerative diseases. In horses, specific and sensitive assays for IL-1β are crucial for immunological research on inflammatory processes and diseases. In this article, we describe the development of four monoclonal antibodies (mAbs) against equine IL-1β. The specificity of the new IL-1β mAbs was confirmed using a panel of equine recombinant cytokines and chemok...
Monitoring of inflammatory blood biomarkers in foals with Rhodococcus Equi pneumonia during antimicrobial treatment. Rhodococcus equi (R. equi), a gram-positive facultative intracellular pathogen, is a common cause of pneumonia in foals and represents a major cause of disease and death. The aim of the present study was to investigate the time-depended changes in White Blood Cells (WBC), basophils (Baso), neutrophils (Neu), lymphocytes (Lymf), monocytes (Mon), eosinophils (Eos), platelet (PLT) counts, fibrinogen (Fbg) concentration, interferon (IFN-α, IFN-γ) and interleukins (IL-2 and IL-10) in foals with clinical R. equi pneumonia. The main treatment was with azithromycin-rifampicin for 14 days. Blood was ...
Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses. Herpesviruses establish a well-adapted balance with their host's immune system. Despite this co-evolutionary balance, infections can lead to severe disease including neurological disorders in their natural host. In horses, equine herpesvirus 1 (EHV-1) causes respiratory disease, abortions, neonatal foal death and myeloencephalopathy (EHM) in ~10 % of acute infections worldwide. Many aspects of EHM pathogenesis and protection from EHM are still poorly understood. However, it has been shown that the incidence of EHM increases to >70 % in female horses >20 years of age. In this study ...
Interleukin-6 upregulates extracellular matrix gene expression and transforming growth factor β1 activity of tendon progenitor cells. Prolonged inflammation during tendon healing and poor intrinsic healing capacity of tendon are causal factors associated with tendon structural and functional degeneration. Tendon cells, consisting of mature tenocytes and tendon progenitor cells (TPC) function to maintain tendon structure via extracellular matrix (ECM) synthesis. Tendon cells can succumb to tissue cytokine/chemokine alterations during healing and consequently contribute to tendon degeneration. Interleukin-(IL-)1β, IL-6 and TNFα are key cytokines upregulated in injured tendons; the specific effects of IL-6 on flexor tendon-de...
Targeting eosinophils by active vaccination against interleukin-5 reduces basophil counts in horses with insect bite hypersensitivity in the 2nd year of vaccination Previously, virus-like particle (VLP)-based self-vaccinations targeting interleukin (IL)-5 or IL-31 have been suggested to treat equine insect bite hypersensitivity (IBH), a seasonal recurrent allergic dermatitis in horses. The IL-5-targeting equine vaccine significantly reduced blood eosinophil counts in horses, similar to human monoclonal antibodies targeting IL-5 or the IL-5 receptor alpha (IL-5Rα). Previous studies in humans have also reported an additional effect on reduction of basophil counts. The aim of the present study was to evaluate whether an equine anti-IL-5 vaccine affected blo...
Interleukin 5-dependent inflammatory eosinophil subtype involved in allergic insect bite hypersensitivity of horses. Eosinophils are known to play a crucial role in equine insect bite hypersensitivity (IBH), an allergic and pruritic dermatitis. Given the relevant role of eosinophils in disease pathology, a virus-like particle (VLP)-based vaccination targeting equine Interleukin (eIL)-5 has been shown to significantly reduce eosinophil levels in the blood and hence reduced IBH symptoms in horses. The aim of the present study was to assess the presence of different eosinophil subtypes in horses, describe characteristics of these subtypes and evaluate the effect of eIL-5-CuMVTT vaccination on these subtypes. Th...
Botulinum neurotoxin type A does not exert concentration-dependent effects on equine articular cartilage in vitro. To determine whether Botulinum neurotoxin type A (BoNT-A) ameliorates the effects of interleukin 1 (IL-1) on equine articular cartilage, or exerts negative effects on normal equine articular cartilage homeostasis in vitro. Methods: Articular cartilage explants from 6 healthy femoropatellar joints of 3 adult horses. Methods: Explants were allocated to the IL-1 challenged or unchallenged group, then exposed to 1 of 6 concentrations of BoNT-A (0, 1, 10, 50, 100, or 500 pg/mL) for 96 hours. To assess BoNT-A's effects on inflammation, prostaglandin E2 (PGE2) was measured in media via ELISA. Matrix ...
Equine Bone Marrow Aspirate Concentrate. Bone marrow concentrate is generated by centrifugation of bone marrow aspirate. It contains mesenchymal stromal cells, anabolic chemokines/cytokines, and supraphysiological concentrations of interleukin-1 receptor antagonist protein (IL-1RA). It is an effective treatment for osteoarthritis or desmitis, or as an adjunct in surgery to enhance bone or cartilage repair.
Culture Media Supplemented With 10% Equine Serum Provided Chondroprotection in an In Vitro Co-Culture of Cartilage and Synovial Membrane. No studies have evaluated the effect of culture in serum-free media (SF) vs. media supplemented with equine serum (ES) on co-culture of synovial membrane and cartilage tissue explants. The study objective was to evaluate the effects of equine serum supplementation on induced production of inflammatory and catabolic mediators from articular cartilage and synovial explants while in co-culture. Articular cartilage and synovial membrane explants were harvested from femoropatellar joints of five adult horses. Cartilage and synovial explants were harvested from the stifle of five horses, placed in c...
Exogenous interleukin-1 beta stimulation regulates equine tenocyte function and gene expression in three-dimensional culture which can be rescued by pharmacological inhibition of interleukin 1 receptor, but not nuclear factor kappa B, signaling. We investigated how Interleukin 1 beta (IL-1β) impacts equine tenocyte function and global gene expression in vitro and determined if these effects could be rescued by pharmacologically inhibiting nuclear factor-κB (NF-B) or interleukin 1 signalling. Equine superficial digital flexor tenocytes were cultured in three-dimensional (3D) collagen gels and stimulated with IL-1β for two-weeks, with gel contraction and interleukin 6 (IL6) measured throughout and transcriptomic analysis performed at day 14. The impact of three NF-B inhibitors on gel contraction and IL6 secretion were measured in 3D ...
In vitro effects of monophosphoryl lipid A and Poly I:C combination on equine cells. Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. Objective: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). Methods: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination...
Characteristic Inflammatory Biomarkers in an Equine Model of Persistent Synovitis Induced By the Intra-Articular Administration of Monoiodoacetic Acid. Persistent synovitis damages the articular cartilage in horses. To evaluate the effectiveness of treatment for synovitis using a model induced by intra-articular administration of monoiodoacetic acid (MIA), it is necessary to identify inflammatory biomarkers characteristic of the MIA model. Synovitis was induced by administering MIA into the unilateral antebrachiocarpal joints of five horses, and saline was injected into the contralateral joints as a control on day 0. Clinical and ultrasonographic examinations and synovial fluid collection were performed on days 0, 1, 2, 7, 14, 21, 28, and 35....
Equine allergic skin diseases: Clinical consensus guidelines of the World Association for Veterinary Dermatology. Allergic skin diseases are common in horses worldwide. The most common causes are insect bites and environmental allergens. Objective: To review the current literature and provide consensus on pathogenesis, diagnosis, treatment and prevention. Methods: The authors reviewed the literature up to November 2022. Results were presented at North America Veterinary Dermatology Forum (2021) and European Veterinary Dermatology Congress (2021). The report was available to member organisations of the World Association for Veterinary Dermatology for feedback. Conclusions: Insect bite hypersensitivity (IBH...
Transcription of interleukin 31 and its receptor by leukocytes after Culicoides sp stimulation is dose dependent but is not exaggerated in allergic horses or correlated with pruritus. Preliminary evidence supports a role for IL-31 in equine insect bite hypersensitivity (IBH) and pruritus. Our studies investigated IL-31 and IL-31 receptor-α (IL-31RA) transcription in leukocytes from normal and IBH horses in response to Culicoides nubeculosus. 19 normal and 15 IBH horses were recruited in the summer of 2019 (low-dose study) and 8 normal and 10 IBH horses in the winter of 2022 to 2023 (high-dose study). Normal horses had no history or signs of allergic skin disease, while IBH horses had a history and clinical signs compatible with IBH. Pruritus was scored using a visual analo...
The relationship between Th1/Th2 cytokine polarization and milk composition in the postnatal period in Kyrgyz mares and foals. Immune compatibility between mare and foal is one of the important topics of reproductive immunology. At this point, although there are many studies on antibodies, there are not many publications on the relationship between the cytokine levels of mare, foal and milk and the effects of milk composition on this relationship. Here we investigate the relationship between Th1/Th2 cytokine balance and milk composition in Kyrgyz mares and foals. Samples were taken soon after the foal was born and on days 5, 10 and 20 after birth. Th1 (IFN-γ, IL-2, TNF-α) and Th2 (IL-4, IL-5, IL-10) cytokine levels ...
Interleukin-1β and methylprednisolone acetate demonstrate differential effects on equine deep digital flexor tendon and navicular bone fibrocartilage cells in vitro. To investigate the effects of interleukin-1β (IL-1β) and methylprednisolone acetate (MPA) on equine intrabursal deep digital flexor tendon (DDFT) and navicular bone fibrocartilage (NBF) cells in vitro. Methods: Third passage DDFT and NBF cells from 5 healthy donor horses ages 11-17 years euthanized for reasons unrelated to musculoskeletal conditions. Methods: Aggregate cultures were incubated with culture medium alone (control), 10 ng/mL IL-1β, 10 ng/mL IL-1β + 0.05 mg/mL MPA, or 10 ng/mL IL-1β + 0.5 mg/mL MPA for 24 hours. Extracellular matrix (ECM) gene expressions were assessed via rea...
Development of an inhibiting antibody against equine interleukin 5 to treat insect bite hypersensitivity of horses. Insect bite hypersensitivity (IBH) is the most common allergic skin disease of horses. It is caused by insect bites of the Culicoides spp. which mediate a type I/IVb allergy with strong involvement of eosinophil cells. No specific treatment option is available so far. One concept could be the use of a therapeutic antibody targeting equine interleukin 5, the main activator and regulator of eosinophils. Therefore, antibodies were selected by phage display using the naïve human antibody gene libraries HAL9/10, tested in a cellular in vitro inhibition assay and subjected to an in vitro affinity...
Cytokines in equine platelet lysate and related blood products. In equine medicine, the use of regenerative therapeutics has gained growing attention, but is still a new and complex field with room for improvement. Platelet lysate (PL) can be used as therapeutic agent but is also a promising supplement for the culture of multipotent mesenchymal stromal cells. To enable a targeted use of PL both in clinic and laboratory, it is crucial to learn more details on its effective ingredients. While so far, mainly growth factor components have been analyzed in platelet-based products such as PL, the current study focuses on the content of cytokines in serum, plasma...
Cytokine enrichment in equine conditioned serum is not reliant on incubation in specialized containers. Autologous conditioned serum (ACS), i.e serum enriched with anti-inflammatory cytokines and growth factors, is a popular orthobiologic therapy used in equine practice. Costly specialized tubes containing glass beads are commonly used for ACS production. The objective of this in vitro study was to compare cytokine and growth factor levels in equine serum after incubation in three different tubes: commercial plastic ACS tubes (COMM); sterile 50 ml plastic centrifugation tubes (CEN); and 10 ml plastic vacutainer tubes (VAC). Blood from 15 healthy horses was incubated in the different tubes at 3...
Distinct differences in immunological properties of equine orthobiologics revealed by functional and transcriptomic analysis using an activated macrophage readout system. Multiple biological therapies for orthopedic injuries are marketed to veterinarians, despite a lack of rigorous comparative biological activity data to guide informed decisions in selecting a most effective compound. Therefore, the goal of this study was to use relevant bioassay systems to directly compare the anti-inflammatory and immunomodulatory activity of three commonly used orthobiological therapies (OTs): mesenchymal stromal cells (MSC), autologous conditioned serum (ACS), and platelet rich plasma (PRP). Unassigned: Equine monocyte-derived macrophages were used as the readout system to ...
T Helper 17-Like Regulatory T Cells in Equine Synovial Fluid Are Associated With Disease Severity of Naturally Occurring Posttraumatic Osteoarthritis. Infiltration of cluster of differentiation (CD) 3 (CD3) T cells into the synovium and synovial fluid occurs in most patients with posttraumatic osteoarthritis. During disease progression, proinflammatory T helper 17 cells and anti-inflammatory regulatory T cells infiltrate the joint in response to inflammation. This study aimed to characterize the dynamics of regulatory T and T helper 17 cell populations in synovial fluid from equine clinical patients with posttraumatic osteoarthritis to determine whether phenotype and function are associated with potential immunotherapeutic targets. An imbala...
Concurrent versus delayed exposure to corticosteroids in equine articular tissues cultured with local anesthetic. To determine the effect of concurrent versus delayed treatment with corticosteroid on equine articular tissues also treated with local anesthetic in vitro in the presence of inflammatory mediators. Methods: Controlled laboratory study. Methods: Five geldings, one mare (aged 3-18 years). Methods: From each horse, 24 synovial and 12 osteochondral explants were cultured in a 12-well plate (2 wells/group, 2 synovial and 1 osteochondral explant/well, total 216 explants in the study). Explants were stimulated in culture medium with 10 μg/ml recombinant equine interleukin-1β and 10 μg/ml tumor...
Tumour necrosis factor alpha, interleukin 1 beta and interferon gamma have detrimental effects on equine tenocytes that cannot be rescued by IL-1RA or mesenchymal stromal cell-derived factors. Tendon injuries occur commonly in both human and equine athletes, and poor tendon regeneration leads to functionally deficient scar tissue and an increased frequency of re-injury. Despite evidence suggesting inadequate resolution of inflammation leads to fibrotic healing, our understanding of the inflammatory pathways implicated in tendinopathy remains poorly understood, meaning successful targeted treatments are lacking. Here, we demonstrate IL-1β, TNFα and IFN-γ work synergistically to induce greater detrimental consequences for equine tenocytes than when used individually. This includes ...
Changes in novel anti-infalmmatory cytokine concetration in the bood of endurance and race horses at different levels of training. Several anti-inflammatory cytokines have been proposed as markers for exercise monitoring in humans such as the interleukin 1 receptor agonist (IL-ra), or interleukin 13 (IL-13). Equine athletes may be considered a model for human exercise physiology research, however there is a lack of such studies of this species. Thus, we decided to examine the changes of IL-1ra and IL-13 in serum concentration during aerobic (endurance) and anaerobic (race) exercise in horses of different fitness levels in comparison with the well-known anti-inflammatory cytokine interleukin 10 (IL-10). The group of endura...
Intratesticular Versus Intrafunicular Lidocaine to Reduce Perioperative Nociception and Immunological Response in Ponies Undergoing Field Castration. The aim of this study was to evaluate the impact of intratesticular or intrafunicular lidocaine to reduce perioperative nociception and cytokine release in ponies undergoing field castration under total intravenous anaesthesia. Before castration, one group was injected with intrafunicular (FL) lidocaine and the other received intratesticular (TL) lidocaine. All ponies were premedicated with acepromazine (0.05 mg/kg) intramuscularly. Twenty minutes after the administration of acepromazine, xylazine (1 mg/kg) and butorphanol (0.02 mg/kg) were administered intravenously. Lidocaine 2% was given 1 ...
Effects of Crude Rice Bran Oil and a Flaxseed Oil Blend in Young Horses Engaged in a Training Program. Rice bran oil and flaxseed oil contain omega-3 fatty acids with the potential to reduce post-exercise inflammation and muscle damage. This study measures plasma interleukin-1β and creatine kinase and fatty acid profiles in lightly worked, young horses (Equus caballus) undergoing an exercise test after 60 days (d) of oil consumption, where the oil replaced 25% of concentrate calories. Treatments consisted of CON (no oil), FLAX (flaxseed oil blend), and RICE (crude rice bran oil). Blood was collected pre-exercise, and again at 1 min, 30 min, 24 h, 48 h, and 72 h post-IET. Data were analyzed by ...
Effect of different adjuvant formulations on the antibody response of horses to porcine zona pellucida proteins. Immunization with porcine zona pellucida (PZP) proteins is being used successfully to induce infertility in wildlife including horses. However, widespread adoption of this method to control the growth of horse populations requires further refinement in order to induce long-term infertility, reduce the frequency and severity of injection site reactions, and make the vaccines easier to administer. The next generation of PZP-based vaccines will likely be a controlled-release formulation with different adjuvants from the Freund's adjuvants used in existing vaccines. We evaluated the response of eq...
Characterization of the Proteins Secreted by Equine Muscle-Derived Mesenchymal Stem Cells Exposed to Cartilage Explants in Osteoarthritis Model. Osteoarthritis (OA) is a highly prevalent joint degenerative disease for which therapeutic treatments are limited or invasive. Cell therapy based on mesenchymal stem/stromal cells (MSCs) is therefore seen as a promising approach for this disease, in both human and horses. As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study was to characterize the secreted proteins of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the putative clinical interest of mdMSCs as cell therapy for joint diseases like osteoarthritis. An equine ost...
