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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.
Characterisation of the inflammatory cytokine response to anthelmintic treatment in ponies. Anthelmintic treatments have been associated with local inflammatory reactions. Since each class of anthelmintic has unique mechanisms of action affecting different subpopulations of parasites, we hypothesised that they will also induce characteristic proinflammatory responses. Objective: To determine the effect of anthelmintic class on the proinflammatory response post treatment. Methods: Ponies naturally infected with cyathostomins and other parasites after pasture grazing were left untreated or treated with representatives of 3 different classes of anthelmintics: fenbendazole (benzimidazole...
Surgical stress influences cytokine content in autologous conditioned serum. No recommendations have been made regarding the relative timing of blood collection for autologous conditioned serum (ACS) preparation and surgical procedures. Objective: 1) To identify effects of surgical stress on cytokine levels in ACS, 2) identify haematological markers for prediction of cytokine production in ACS and 3) investigate the necessity for specialised ACS containers when preparing a cytokine-rich serum. Methods: Experimental in vitro study. Methods: Blood was drawn from 15 stallions admitted for elective castration preoperatively and 22-24 h post operatively and incubated in A...
Immediate-early protein of equid herpesvirus type 1 as a target for cytotoxic T-lymphocytes in the Thoroughbred horse. Cytotoxic T-lymphocytes (CTLs) are associated with protective immunity against disease caused by equid herpesvirus type 1 (EHV-1). However, the EHV-1 target proteins for CTLs are poorly defined. This limits the development of vaccine candidates designed to stimulate strong CTL immunity. Here, classical CTL assays using lymphocytes from horses of three defined MHC class I types that experienced natural infection with EHV-1 and a modified vaccinia virus construct containing an EHV-1 gene encoding the immediate-early (IE) protein are reported. Horses homozygous for the equine leukocyte antigen (E...
The effect of treatment with immune modulators on endometrial cytokine expression in mares susceptible to persistent breeding-induced endometritis. Research has shown that 6 h after breeding is a critical time during the uterine innate immune response, and the failure to respond appropriately will result in persistent breeding-induced endometritis. This presents a potential opportunity to modulate the course of inflammation towards a timely resolution. Objective: To evaluate the effects of immune modulation on endometrial mRNA expression of inflammatory genes in susceptible mares 6 h after breeding. The hypothesis was that immune modulation alters endometrial cytokine expression in susceptible mares. Methods: A randomised controlled s...
Major histocompatibility complex I mediates immunological tolerance of the trophoblast during pregnancy and may mediate rejection during parturition. During pregnancy in larger mammals, the maternal immune system must tolerate the fetus for months while resisting external infection. This tolerance is facilitated by immunological communication between the fetus and the mother, which is mediated by Major Histocompatibility Complex I (MHC I) proteins, by leukocytes, and by the cytokines secreted by the leukocytes. Fetal-maternal immunological communication also supports pregnancy by inducing physiological changes in the mother. If the mother "misunderstands" the signal sent by the fetus during pregnancy, the fetus will be miscarried or deliver...
Effects of age and macrophage lineage on intracellular survival and cytokine induction after infection with Rhodococcus equi. Rhodococcus equi, a facultative intracellular pathogen of macrophages, causes life-threatening pneumonia in foals and in people with underlying immune deficiencies. As a basis for this study, we hypothesized that macrophage lineage and age would affect intracellular survival of R. equi and cytokine induction after infection. Monocyte-derived and bronchoalveolar macrophages from 10 adult horses and from 10 foals (sampled at 1-3 days, 2 weeks, 1 month, 3 months, and 5 months of age) were infected ex vivo with virulent R. equi. Intracellular R. equi were quantified and mRNA expression of IL-1β, ...
Immunology of infective preterm delivery in the mare. Placentitis is reported to be the cause of 9.8-33.5% of abortions, stillbirths and perinatal losses in horses. Bacterial infections are responsible for 53% of placentitis cases with Streptococcus equi ssp. zooepidemicus being isolated in 28% of these cases. Clinically, mares may have a vaginal discharge, show udder development, lactate prenatally and deliver a premature or dead foal. Major aspects of the pathogenesis of infectious preterm delivery that may require more effective therapeutic targeting are myometrial contraction, immunological aspects of preterm delivery, and the effects of proi...
Ovarian steroid-dependent tumor necrosis factor-α production and its action on the equine endometrium in vitro. Tumor necrosis factor-α (TNF) is a cytokine that plays important roles in functions of the endometrium. The aims of this study were to determine whether (i) ovarian steroids modulate TNF production by endometrial cells (Experiment 1); (ii) TNF effects on prostaglandin (PG) production in cultured equine endometrial cells and tissue (Experiment 2). Epithelial and stromal cells were isolated from equine endometrium (Days 2-5 of the estrous cycle; n=20) and treated after passage 1. In Experiment 1, epithelial and stromal cells were exposed to progesterone (P4; 10(-7)M), 17-β estradiol (E2; 10(-9...
Equine mesenchymal stem cells inhibit T cell proliferation through different mechanisms depending on tissue source. Mesenchymal stem cells (MSCs) are used in both human clinical trials and veterinary medicine for the treatment of inflammatory and immune-mediated diseases. MSCs modulate inflammation by decreasing the cells and products of the inflammatory response. Stimulated equine MSCs from bone marrow (BM), adipose tissue (AT), cord blood (CB), and umbilical cord tissue (CT) inhibit lymphocyte proliferation and decrease inflammatory cytokine production. We hypothesized that equine MSCs inhibit T cell proliferation through secreted mediators and that MSCs from different tissue sources decrease T cell proli...
Use of mesenchymal stem cells or autologous conditioned serum to modulate the inflammatory response to spermatozoa in mares. Current treatments for Persistent mating-induced endometritis such as uterine lavage and oxytocin therapy focus on aiding the uterus in removal of inflammatory products, but these treatments do not modulate the inciting inflammatory response. Biological treatments, such as autologous conditioned serum (ACS) and mesenchymal stem cells (MSCs), have been used in human and veterinary medicine for immunomodulation for over 10 years. The objectives of this project were to evaluate the ability of ACS or MSCs to modulate the inflammatory response to spermatozoa after breeding. Two experiments were pe...
Interleukin-1β inhibits synthesis of 5-lipooxygenase in lipopolysaccharide-stimulated equine whole blood. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine. It induces the synthesis of prostaglandin E2 (PGE2) catalyzed by cyclooxygenase (COX) and microsomal prostaglandin E synthase (m-PGES). Besides its pro-inflammatory properties, PGE2 also exhibits anti-inflammatory properties by inhibiting synthesis of 5-lipooxygenase (5-LO) products which are in themselves, pro-inflammatory mediators. Thus, inhibition of 5-LO products is beneficial in regulating immune-responses and pro-inflammatory processes. To investigate the hypothesis that IL-1β is responsible for the increase in the synthesis of P...
The effect of equine metabolic syndrome on the ovarian follicular environment. Obesity in many species is associated with reduced fertility and increased risk of metabolic disorders and cardiovascular dysfunction in offspring. Equine metabolic syndrome (EMS) is associated with obesity and characterized by insulin resistance, decreased adiponectin, and elevated insulin, leptin, and pro-inflammatory cytokines. These alterations can potentially disrupt follicular development and impair fertility. We hypothesized that mares with EMS have an altered follicular environment when compared to their normal counterparts, affecting gene regulation for follicle and oocyte maturation....
A comparison of pro-inflammatory cytokine mRNA expression in equine bronchoalveolar lavage (BAL) and peripheral blood. An imbalance in various cytokine mRNA expression in bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) in horses suffering from recurrent airway obstruction (RAO) has been demonstrated; however, the natural variation of cytokine expression in healthy horses has yet to be described. The objectives of this study were to: (1) identify age-related differences in the expression of pro-inflammatory cytokines in BAL and PBMC, (2) compare the expression of pro-inflammatory cytokines between BAL and PBMC, and (3) evaluate the relationship between BAL pro-inflammatory cytokine ex...
Training modifies innate immune responses in blood monocytes and in pulmonary alveolar macrophages. In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs) and costimulatory and antigen-presenting molecules. Lower airway diseases are also a common problem in sport and racing horses. Because innate immunity plays an essential role in lung defense mechanisms, we assessed the effect of acute exercise and training on innate immune responses in two different compartments. Blood monocytes and pulmonary alveolar macrophages (PAMs) were collected from horses in untrained, moderately trained, inten...
Effects of interleukin-6 and interleukin-1β on expression of growth differentiation factor-5 and Wnt signaling pathway genes in equine chondrocytes. To determine the effects of interleukin (IL)-6 and IL-1β stimulation on expression of growth differentiation factor (GDF)-5 and Wnt signaling pathway genes in equine chondrocytes. Methods: Macroscopically normal articular cartilage samples from 6 horses and osteochondral fragments (OCFs) from 3 horses. Methods: Chondrocyte pellets were prepared and cultured without stimulation or following stimulation with IL-6 or IL-1β for 1, 2, 12, and 48 hours; expression of GDF-5 was determined with a quantitative real-time PCR assay. Expression of genes in various signaling pathways was determined with ...
Comparison of antibody and cell-mediated immune responses of foals and adult horses after vaccination with live Mycobacterium bovis BCG. Equine neonates have reduced humoral and cell-mediated immune responses compared to adult horses after administration of killed vaccines. As a basis for this study, we hypothesized that newborn foals can mount strong immune responses after vaccination with live Mycobacterium bovis BCG. Methods: Healthy 4-day-old foals (n=7), 4-month-old foals (n=7) and adult horses (n=6) were vaccinated once with live M. bovis BCG. Age-matched animals (n=5 per group) were used as unvaccinated controls. Relative vaccine-specific immunoglobulin concentrations and whole blood mRNA expression of IFN-γ, IL-4, and ...
Analyses of lipid rafts, Toll-like receptors 2 and 4, and cytokines in foals vaccinated with Virulence Associated Protein A/CpG oligonucleotide vaccine against Rhodococcus equi. Rhodococcus equi establishes long-term pulmonary infection, survives in phagolysosomes of alveolar macrophages and causes pneumonia in foals. The failure of the foal to clear R. equi bacteria is believed to be due to its inability to produce IFN-γ and defects in Toll-like receptor(TLR) signaling. Lipid rafts sequester immune receptors such as TLRs and facilitate efficient cell signaling and therefore, a deficiency in accumulation of receptors in lipid rafts may result in failure to activate. We tested whether a Virulence Associated Protein A (VapA)/CpG vaccine against R. equi would impact the...
Proteomic analysis of tendon extracellular matrix reveals disease stage-specific fragmentation and differential cleavage of COMP (cartilage oligomeric matrix protein). During inflammatory processes the extracellular matrix (ECM) is extensively remodeled, and many of the constituent components are released as proteolytically cleaved fragments. These degradative processes are better documented for inflammatory joint diseases than tendinopathy even though the pathogenesis has many similarities. The aims of this study were to investigate the proteomic composition of injured tendons during early and late disease stages to identify disease-specific cleavage patterns of the ECM protein cartilage oligomeric matrix protein (COMP). In addition to characterizing fragme...
Carprofen inhibits the release of matrix metalloproteinases 1, 3, and 13 in the secretome of an explant model of articular cartilage stimulated with interleukin 1β. Arthritic diseases are characterized by the degradation of collagenous and noncollagenous extracellular matrix (ECM) components in articular cartilage. The increased expression and activity of matrix metalloproteinases (MMPs) is partly responsible for cartilage degradation. This study used proteomics to identify inflammatory proteins and catabolic enzymes released in a serum-free explant model of articular cartilage stimulated with the pro-inflammatory cytokine interleukin 1β (IL-1β). Western blotting was used to quantify the release of selected proteins in the presence or absence of the cyc...
Toll-like receptor and pro-inflammatory cytokine expression during prolonged hyperinsulinaemia in horses: implications for laminitis. Equine laminitis, a disease of the lamellar structure of the horse's hoof, can be incited by numerous factors that include inflammatory and metabolic aetiologies. However, the role of inflammation in hyperinsulinaemic laminitis has not been adequately defined. Toll-like receptor (TLR) activation results in up-regulation of inflammatory pathways and the release of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), and may be a pathogenic factor in laminitis. The aim of this study was to determine whether TLR4 expression and subsequent pro-infla...
Real time RT-PCR analysis of inflammatory mediator expression in recurrent airway obstruction-affected horses. The goal of the present study was to investigate mRNA expression levels of several cytokines and inflammatory mediators in broncho-alveolar lavage (BAL) fluid and respiratory epithelium in recurrent airway obstruction (RAO)-affected horses. RAO, also called heaves, is a common, performance-limiting, equine respiratory disease with clinical signs and pathophysiological similarities to human asthma, and characterized by bronchospasm, neutrophilic infiltration and increased mucus in the airways. Six RAO-affected horses were examined twice within 15 days and seven clinically healthy horses were ex...
Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses. To compare the clinical and inflammatory joint responses to intra-articular injection of bone marrow-derived mesenchymal stem cells (MSC) including autologous, genetically modified autologous, allogeneic, or xenogeneic cells in horses. Methods: Six five-year-old Thoroughbred mares had one fetlock joint injected with Gey's balanced salt solution as the vehicle control. Each fetlock joint of each horse was subsequently injected with 15 million MSC from the described MSC groups, and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, joint swelling, and pain...
Evaluation of antioxidant capacity and inflammatory cytokine gene expression in horses fed silibinin complexed with phospholipid. To evaluate antioxidant capacity and inflammatory cytokine gene expression in horses fed silibinin complexed with phospholipid. Methods: 5 healthy horses. Methods: Horses consumed increasing orally administered doses of silibinin phospholipid during 4 nonconsecutive weeks (0 mg/kg, 6.5 mg/kg, 13 mg/kg, and 26 mg/kg of body weight, twice daily for 7 days each week). Dose-related changes in plasma antioxidant capacity, peripheral blood cell glutathione concentration and antioxidant enzyme activities, and blood cytokine gene expression were evaluated. Results: Plasma antioxidant capacity increase...
Evaluation of the reactivity of commercially available monoclonal antibodies with equine cytokines. Research on equine cytokines is often performed by analyses of mRNA. For many equine cytokines an analysis on the actual protein level is limited by the availability of antibodies against the targeted cytokines. Generation of new antibodies is ongoing but time consuming. Thus, testing the reactivity of commercially available antibodies for cross-reactivity with equine cytokines is of particular interest. Fifteen monoclonal antibodies against IL-1β, IL-6, IL-8, IL-12, IL-18 and Granulocyte Macrophage Colony stimulating factor (GM-CSF) of different species were evaluated for reactivity with the...
Investigation of the immune response to autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses. Mesenchymal stem cells have demonstrated immunomodulatory capabilities as well as modest efficacy in animal models of joint injury, warranting further study as a potential treatment of joint disease. The goal of the study was to investigate the blood and synovial immune and histologic response to intra-articular injection of autologous, allogeneic, and xenogeneic bone marrow-derived mesenchymal stem cells (MSC) in horses. The study group consisted of 6 five-year-old Thoroughbred mares that had been injected previously with 15 million, genetically modified autologous, allogeneic, or xenogeneic ...
Fibroblast growth factor-2 expression in the preimplantation equine conceptus and endometrium of pregnant and cyclic mares. Uterine-derived growth factors and cytokines play essential roles in regulating preimplantation conceptus development. In several species, fibroblast growth factor-2 (FGF2) promotes embryogenesis, trophoblast cell migration, and adhesion. This study investigated mRNA expression for FGF2, its receptors (FGFR1-4), the activating factor FGF binding protein (FGF-BP) in equine endometrium and trophectoderm during early pregnancy and the estrous cycle, and localized FGF2 protein in both endometrium and conceptus tissues. FGF2, FGFRs1-4, and FGFBP mRNAs were expressed in endometrium throughout the es...
Humoral response and antiviral cytokine expression following vaccination of thoroughbred weanlings–a blinded comparison of commercially available vaccines. Previous studies in experimental ponies using interferon gamma (IFN-γ) as a marker for cell mediated immune (CMI) response demonstrated an increase in IFN-γ gene expression following vaccination with an ISCOM subunit, a canarypox recombinant and more recently, an inactivated whole virus vaccine. The objective of this study was to carry out an independent comparison of both humoral antibody and CMI responses elicited following vaccination with all these vaccine presentation systems. Antibody response of 44 Thoroughbred weanlings was monitored for three weeks following the second dose of prima...
Differential CD4+ T-cell responses of allergic and non-allergic subjects to the immunodominant epitope region of the horse major allergen Equ c 1. The responses of allergen-specific CD4(+) T cells of allergic and healthy individuals are still incompletely understood. Our objective was to investigate the functional and phenotypic properties of CD4(+) T cells of horse-allergic and healthy subjects specific to the immunodominant epitope region of the major horse allergen Equ c 1. Specific T-cell lines (TCLs) and clones were generated from peripheral blood mononuclear cells with Equ c 1(143-160), the peptide containing the immunodominant epitope region of Equ c 1. The frequency, proliferative response, cytokine production and HLA restriction...
Synovial fluid growth factor and cytokine concentrations after intra-articular injection of a platelet-rich product in horses. Platelet-rich plasma (PRP) products may be useful for treatment of joint disease in horses, but may contain undesirable pro-inflammatory cytokines in addition to growth factors. This study investigated whether autologous PRP increases synovial fluid growth factor and cytokine concentrations when injected into normal equine metacarpophalangeal and metatarsophalangeal (fetlock) joints. Fetlock joints of seven healthy horses received one of four treatments: saline, resting PRP, CaCl2-activated PRP or thrombin-activated PRP. Synovial fluid was sampled prior to injection and at 6, 24, 48 and 96 h p...
Role of tumor necrosis factor-α, interferon-γ and Fas-ligand on in vitro nitric oxide activity in the corpus luteum. Normal reproductive function involves the expression of inflammatory mediators. Regarding the corpus luteum (CL), cytokines promote the cross-talk between immune, vascular and steroidogenic cells, among others. Moreover, TNF, IFNG and FASL were shown to regulate equine CL establishment and regression. We hypothesized that cytokines action on equine CL may be mediated by nitric oxide (NO), through the regulation of endothelial NO synthase (eNOS) expression. TNF increased eNOS mRNA level and NO metabolite (nitrite) production during CL growth. Cytokines combined action (TNF+IFNG+FASL) promoted e...
