Omneity® Pellets
All-In-One Vitamin & Mineral Pellet
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.
Disparate effects of LPS infusion and carbohydrate overload on inflammatory gene expression in equine laminae. Although clinical evidence of endotoxemia has been associated with the development of acute laminitis in hospitalized horses with gastrointestinal diseases and endotoxins have been detected in the circulation of horses with experimentally-induced laminitis, it is unclear what role, if any, endotoxins have play the pathogenesis of the disease. Therefore, in the present study we compared the effects of endotoxin infusion to that of intra-gastric administration of mixed carbohydrate (CHO) on clinical signs of laminitis, plasma concentrations of TNF-α and IL-10, and laminar tissue expression of 2...
Experimental model of equine alveolar macrophage stimulation with TLR ligands. Pulmonary diseases are common in horses and have a major economic impact on the equine industry. Some of them could be associated with an inadequate immune response in the lung, but methods to evaluate this response in horses are lacking. The aim of this study was to develop and validate an experimental model that could be applied in several physiological and pathological conditions to assess the innate immune response of equine pulmonary cells. Equine alveolar macrophages (AMs) obtained from bronchoalveolar lavages were isolated from other cells by adhesion. TLR2, 3, and 4 expression in AMs w...
Inflammatory stimuli differentially modulate the transcription of paracrine signaling molecules of equine bone marrow multipotent mesenchymal stromal cells. Osteoarthritis (OA) is a degenerative disease of joint tissues that causes articular cartilage erosion, osteophytosis and loss of function due to pain. Inflammation and inflammatory cytokines in synovial fluid (SF) contribute to OA progression. Intra-articular (IA) injections of multipotent mesenchymal stromal cells (MSCs) are employed to treat OA in both humans and animals. MSCs secrete paracrine pro-inflammatory and anabolic signaling molecules that promote tissue repair. The objective of this study was to investigate the effects of OASF on the gene expression of paracrine signaling molecule...
Effects of serum and autologous conditioned serum on equine articular chondrocytes treated with interleukin-1β. To compare the effects of autologous equine serum (AES) and autologous conditioned serum (ACS) on equine articular chondrocyte metabolism when stimulated with recombinant human (rh) interleukin (IL)-1β. Methods: Articular cartilage and nonconditioned and conditioned serum from 6 young adult horses. Methods: Cartilage samples were digested, and chondrocytes were isolated and formed into pellets. Chondrocyte pellets were treated with each of the following: 10% AES, 10% AES and rhIL-1β, 20% AES and rhIL-1β, 10% ACS and rhIL-1β, and 20% ACS and rhIL-1β, and various effects of these treatments...
Endometrial inflammatory markers of the early immune response in mares susceptible or resistant to persistent breeding-induced endometritis. Transient endometritis after breeding is necessary for clearance of bacteria and spermatozoa; however, in a subpopulation of mares, the inflammation fails to resolve in a timely fashion. The objective of this study was to describe the uterine inflammatory response in mares susceptible or resistant to persistent breeding-induced endometritis (PBIE) during the first 24 h after induction of uterine inflammation.Twelve mares were classified as susceptible (nZ6) or resistant (nZ6) to PBIE. Mares were inseminated over five estrous cycles and endometrial biopsies were collected at one time point per ...
Establishment and evaluation of a bead-based luminex assay allowing simultaneous quantification of equine IL-12 and IFN-γ. Interleukin-12 (IL-12) and interferon gamma (IFN-γ) are key cytokines in immunemediated equine melanoma therapy. Currently, a method for accurate simultaneous quantification of these equine cytokines is lacking. Therefore, we sought to establish an assay that allows for accurate and simultaneous quantification of equine IL-12 (eIL-12) and IFN-γ (eIFN-γ). Methods: Several antibodies were evaluated for cross-reactivity to eIL-12 and eIFN-γ and were used to establish a bead-based Luminex assay, which was subsequently applied to quantify cytokine concentrations in biological samples. Results: ...
Effects of selenium source on measures of selenium status and immune function in horses. The effects of selenium (Se) supplementation and source on equine immune function have not been extensively studied. This study examined the effects of oral Se supplementation and Se source on aspects of innate and adaptive immunity in horses. Fifteen horses were assigned to 1 of 3 groups (5 horses/group): control, inorganic Se (sodium selenite), organic Se (Se yeast). Immune function tests performed included: lymphocyte proliferation in response to mitogen concanavalin A, neutrophil phagocytosis, antibody production after rabies vaccination, relative cytokine gene expression in stimulated lym...
Equine colostral carbohydrates reduce lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells. Increasing evidence suggests that reactions to lipopolysaccharide (LPS), particularly in the gut, can be partly or completely mitigated by colostrum- and milk-derived oligosaccharides. Confirmation of this hypothesis could lead to the development of new therapeutic concepts. Objective: To demonstrate the influence of equine colostral carbohydrates on the inflammatory response in an in vitro model with equine peripheral blood mononuclear cells (PBMCs). Methods: Carbohydrates were extracted from mare colostrum, and then evaluated for their influence on LPS-induced inflammatory responses in PBMCs...
Plasma concentrations of inflammatory markers in previously laminitic ponies. The mechanisms underlying individual animal predisposition to pasture-associated laminitis remain unclear; however, chronic inflammation is implicated. Objective: To identify differences in the inflammatory profile of a group of previously laminitic ponies compared with control animals at pasture in late spring and winter. Methods: Previously laminitic (PL; n = 38 and 42) and nonlaminitic control ponies (NL; n = 41 and 39) were sampled in late spring and winter. Body condition score, height, weight and crest height and thickness were measured. Plasma concentrations of tumour necrosis factor-α...
Optimization of scAAVIL-1ra In Vitro and In Vivo to Deliver High Levels of Therapeutic Protein for Treatment of Osteoarthritis. Osteoarthritis (OA) affects over 40 million people annually. We evaluated interleukin-1 receptor antagonist (IL-1ra) gene transfer in an equine model based on IL-1ra protein therapy which inhibits inflammation through blocking IL-1. Using the self-complementary adeno-associated virus (scAAV)IL-1ra equine gene as a starting construct, we optimized the transgene cassette by analyzing promoters (cytomegalovirus (CMV) versus chicken β-actin hybrid (CBh)), coding sequences (optimized versus unoptimized), vector capsid (serotype 2 versus chimeric capsid), and biological activity in vitro. AAV serot...
Influence of corticosteroids on interleukin-1β-stimulated equine chondrocyte gene expression. To compare the effects of triamcinolone acetonide (TA) and methylprednisolone acetate (MPA) on expression of selected chondrocyte genes in recombinant equine interleukin-1β (reIL-1β) stimulated articular cartilage explants. Methods: In vitro experiment. Methods: Horses (n = 6). Methods: Articular cartilage explants from 2- to 3- year-old horses were exposed to reIL-1β in the presence and absence of TA and MPA at 10(-7) and 10(-6) M. Resting levels of mRNA of anabolic and catabolic genes of chondrocyte origin were quantified using qPCR after 6- and 12-hour incubations. Genes of interest incl...
Relationships between body condition score and plasma inflammatory cytokines, insulin, and lipids in a mixed population of light-breed horses. Obesity and hyperinsulinemia increase the risk of laminitis in horses and ponies. In mares, obesity also has been associated with increased circulating concentrations of the proinflammatory cytokine, tumor necrosis factor (TNF)-α. The association of other proinflammatory cytokines with body condition score (BCS) and insulin requires further determination. Objective: Plasma concentrations of TNF, interleukin (IL)-1β, IL-6, and serum amyloid A (SAA) will positively correlate with BCS or insulin or both in horses. Furthermore, inflammatory protein concentrations will correlate with age and vari...
Seasonal differences in cytokine expression in the skin of Shetland ponies suffering from insect bite hypersensitivity. Insect bite hypersensitivity (IBH) in horses is a seasonal, IgE-mediated, pruritic skin disorder primarily caused by Culicoides spp. We hypothesize that a mixed Th2/Th1-type immune status, off season, alters into Th2-dominated immune reactivity in the skin of IBH-affected ponies in the IBH season. To study these immune response patterns Culicoides-specific IgE levels, skin histopathology and cytokine and transcription factor mRNA expression (IL4, IL10, IL13, IFNγ, FoxP3 and CD3(ζ)) in lesional and non-lesional skin of ponies affected by IBH in the IBH season were compared with those of the s...
Characterization of the inflammatory infiltrate and cytokine expression in the skin of horses with recurrent urticaria. Recurrent urticaria (RU) is a common skin disease of horses, but little is known about its pathogenesis. Objective: The aim of this study was to characterize the inflammatory cell infiltrate and cytokine expression pattern in the skin of horses with RU. Methods: Biopsies of lesional and nonlesional skin of horses with RU (n = 8) and of skin from healthy control horses (n = 8) were evaluated. Methods: The inflammatory cell infiltrate was analysed by routine histology. Immunohistochemistry was used to identify T cells (CD3), B ells (CD79), macrophages (MAC387) and mast cells (tryptase). E...
Expression of endometrial immune-related genes possibly functioning during early pregnancy in the mare. Despite enormous efforts, biochemical and molecular mechanisms associated with equine reproduction, particularly processes of pregnancy establishment, have not been well characterized. Previously, PCR-selected suppression subtraction hybridization analysis was executed to identify unique molecules functioning in the equine endometrium during periods of pregnancy establishment, and granzyme B (GZMB) cDNA was found in the pregnant endometrial cDNA library. Because GZMB is produced from natural killer (NK) cells, endometrial expression of GZMB and immune-related transcripts were characterized in ...
Progestin treatment does not affect expression of cytokines, steroid receptors, oxytocin receptor, and cyclooxygenase 2 in fetal membranes and endometrium from pony mares at parturition. In most mammalian species, progestins have a major function in maintaining pregnancy. In humans, the physiologic initiation of parturition bears similarities with inflammatory processes and anti-inflammatory effects of progestins have been suggested to postpone birth until term. To examine if comparable effects exist in the horse, mares were treated with the synthetic progestin altrenogest from day 280 of gestation until parturition (N = 5) or were left untreated as controls (N = 7). Tissue from the amnion (AMN), allantochorion (AC), and endometrium (EM) was collected at foaling and mRNA expre...
Effects of body weight reduction on blood adipokines and subcutaneous adipose tissue adipokine mRNA expression profiles in obese ponies. Fifteen obese ponies were used in a body weight (BW) reduction programme (BWRP, daily energy intake: 7.0-8.4 MJ/100 kg BW). A frequently sampled intravenous glucose tolerance test was used to assess insulin sensitivity. Subcutaneous adipose tissue biopsies of the tail head were obtained for mRNA gene expression profiles of adiponectin, retinol-binding protein 4 (RBP4), interleukin 6 (IL-6) and macrophage activation marker (CD68) before and after BWRP. Blood samples were analysed for serum leptin, serum RBP4 and plasma adiponectin. Significant BW losses occurred with 7 MJ DE/100 kg BW. Serum le...
Concentration-dependent effects of tiludronate on equine articular cartilage explants incubated with and without interleukin-1β. To determine concentration-dependent effects of tiludronate on cartilage explants incubated with or without recombinant equine interleukin-1β (rEq IL-1). Methods: Articular cartilage explants from the femorotibial joints of 3 young adult horses. Methods: Cartilage explants were incubated with 1 of 6 concentrations (0, 0.19, 1.9, 19, 190, or 1,900 mg/L) of tiludronate and with or without rEq IL-1 (0.01 ng/mL) for 96 hours. Prostaglandin E(2) (PGE(2)) concentrations in culture medium and explant digests were analyzed via PGE(2) enzyme immunoassay. Sulfated glycosaminoglycan (sGAG) concentration...
Effect of training status on immune defence related gene expression in Thoroughbred: are genes ready for the sprint? Athletic performance is both a stress factor and an adaptive response to exercise that may be modulated by training, reduce inflammation and help prevent disease. Studies on the endocrinology of exercise and training have demonstrated the existence of an integrated metabolic network of hormone and cytokine regulation. Subsequent molecular studies have shown that repeated bouts of exercise may establish new basal levels of gene expression at rest. The Thoroughbred horse may be a useful 'exercise model' for inter-individual comparisons between subjects with homogeneous genetic and environmental ...
Effects of a “two-hit” model of organ damage on the systemic inflammatory response and development of laminitis in horses. The role of endotoxemia in the development of laminitis remains unclear. Although systemic inflammation is a risk factor for laminitis in hospitalized horses, experimental endotoxin administration fails to induce the disease. While not sufficient to cause laminitis by itself, endotoxemia might predispose laminar tissue to damage from other mediators during systemic inflammation. In "two-hit" models of organ damage, sequential exposure to inflammatory stimuli primes the immune system and causes exaggerated inflammatory responses during sepsis. Acute laminitis shares many characteristics with se...
Ethyl pyruvate diminishes the inflammatory response to lipopolysaccharide infusion in horses. Endotoxaemia contributes to morbidity and mortality in horses with colic due to inflammatory cascade activation. Effective therapeutic interventions are limited for these horses. Ethyl pyruvate (EP), an anti-inflammatory agent that alters the expression of proinflammatory cytokines, improved survival and organ function in sepsis and gastrointestinal injury in rodents and swine. Therapeutic efficacy of EP is unknown in endotoxaemic horses. Objective: Determine the effects of EP on signs of endotoxaemia and expression of proinflammatory cytokines following administration of lipopolysaccharide (L...
Expression of interleukin-1β, interleukin-8, and interferon-γ in blood samples obtained from healthy and sick neonatal foals. To evaluate and compare the gene expression of interleukin(IL)-1β, IL-8, and interferon-γ during the first 72 hours after birth in healthy foals and during the first 72 hours after hospitalization in sick neonatal foals and investigate correlations of clinicopathologic variables with cytokine expressions in healthy and sick neonatal foals. Methods: 33 foals < 7 days old (10 healthy foals, 7 foals with sepsis, 6 foals with peripartum asphyxia syndrome, and 12 foals with other diseases [2 with failure of passive transfer of immunity only were not further evaluated]). Methods: A blood sample...
Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses. To determine whether the method of lipopolysaccharide (LPS) administration (intermittent vs continuous) affects the magnitude and duration of the systemic inflammatory response in horses and whether prolonged (48 hours) endotoxemia induces laminitis. Methods: 12 healthy adult horses (10 mares and 2 geldings). Methods: Horses were randomly assigned to receive LPS (total dose, 80 μg; n = 4) or saline (0.9% NaCl) solution (80 mL/h; 4) via constant rate infusion or 8 bolus IV injections of LPS (10 μg, q 6 h;4) during a 48-hour period. Physical examinations were performed every 4 hours, inflammat...
Evaluation of the inflammatory response in experimentally induced synovitis in the horse: a comparison of recombinant equine interleukin 1 beta and lipopolysaccharide. To compare two transient models of synovitis-osteoarthritis (OA) in horses by characterizing biological changes in synovial fluid and joint tissue. Methods: Twelve skeletally mature mares were utilized in a block design. Synovitis was induced by an intra-articular injection of 100 ng recombinant equine interleukin 1 beta (reIL-1β) or 0.5 ng lipopolysaccharide (LPS) into a middle carpal joint in 1 ml volumes. One ml of saline was injected into the contra-lateral control joint. Lameness evaluations were conducted through post-injection hour (PIH) 8 (at which time arthroscopic removal of syno...
Effects of age and R848 stimulation on expression of Toll-like receptor 8 mRNA by foal neutrophils. The innate immune system plays a critical role in protecting neonates against infections early in life and Toll-like receptors (TLRs) are key components of innate immune recognition of pathogens. This study examined the effects of age and stimulation with a TLR 7/8 agonist (R848) on TLR8 mRNA expression by foal neutrophils during the first month of life. We also examined the effects of R848 stimulation on mRNA expression of interleukin (IL)-6 and IL-8 at 1 and 14 days of life. We observed that TLR8 mRNA was constitutively expressed (P<0.05) at all ages examined, and its expression did not c...
Effect of immunomodulatory therapy on the endometrial inflammatory response to induced infectious endometritis in susceptible mares. The objective of the present study was to evaluate the effect of immunomodulatory therapy (glucocorticoids (GC) and mycobacterium cell wall extract (MCWE)) on the endometrial gene expression of inflammatory cytokines in susceptible mares with induced infectious endometritis. Endometrial gene expression of pro- and anti-inflammatory cytokines; interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (ra), acute phase protein (APP) serum amyloid A (SAA) and clinical parameters were evaluated. Five mares were classified as susceptible to persistent endomet...
Autologous point-of-care cellular therapies variably induce equine mesenchymal stem cell migration, proliferation and cytokine expression. Autologous cellular therapy products including adipose-derived stromal vascular fraction (SVF), bone marrow mononuclear cells (BMMNs), cord blood mononuclear cells (CBMNs) and platelet rich plasma are options for treatment of acute orthopaedic lesions while mesenchymal stem cells (MSCs) are culture expanded. These products may contribute to healing by secreting matrix proteins or growth factors, but they may also act on endogenous MSCs to facilitate healing. Objective: To determine the effects of cell therapy products on MSCs function in vitro. The hypothesis was that cell therapy products pro...
Effects of Platelet-Rich Plasma Composition on Anabolic and Catabolic Activities in Equine Cartilage and Meniscal Explants. To evaluate the effects of single- and double-spin preparations of platelet-rich plasma (PRP) on anabolic and catabolic activities of cartilage and meniscal explants in vitro. Methods: Single- and double-spin PRP was prepared using laboratory processing or commercial kits. The cellular contents were quantified, and each PRP was mixed in equal quantities with cell culture medium and added to cartilage or meniscus explant cultures, with or without interleukin 1 β (IL-1β). Extracellular matrix synthesis was quantified over 24 hours via (35)S-sulfate and (3)H-proline incorporation, while gene ex...
Pulmonary intravascular macrophages as proinflammatory cells in heaves, an asthma-like equine disease. Heaves, an obstructive neutrophilic airway inflammation of horses, is triggered by dust components such as endotoxin and has similarities to human asthma. Pulmonary intravascular macrophages (PIMs) increase horses' sensitivity to endotoxin-induced lung inflammation; however, their role in an airborne pathology remains unknown. Therefore, we investigated the role of PIMs in the development of heaves in horses. Clinical and inflammatory responses were evaluated following induction of heaves by moldy hay exposure and PIM depletion with gadolinium chloride (GC). Mares (N = 9) were exposed to four ...
Increased hypoxia-inducible factor 1α expression in lung cells of horses with recurrent airway obstruction. Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-α in myeloid cells in ho...
