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.
Horses affected by chronic piroplasmosis may develop poor performance and muscle atrophy. Here we investigate the pathological and immunopathological aspects of myopathy occurring in chronic equine piroplasmosis. The study included 16 horses serologically positive for equine piroplasms presenting with clinical signs and supporting serum biochemical evidence of a myopathy. Skeletal muscle was evaluated by histopathology, immunohistochemistry, indirect immunofluorescence, and molecular detection of piroplasms and inflammatory cytokines in skeletal muscle. Histologic lesions included muscle fiber...
Hill JA, Cassano JM, Goodale MB, Fortier LA.OBJECTIVE To determine whether major histocompatability complex (MHC) class II expression in equine mesenchymal stem cells (MSCs) changes with exposure to a proinflammatory environment reflective of an inflamed joint. SAMPLE Cryopreserved bone marrow-derived MSCs from 12 horses and cartilage and synovium samples from 1 horse euthanized for reasons other than lameness. PROCEDURES In part 1 of a 3-part study, the suitability of a quantitative reverse transcriptase PCR (qRT-PCR) assay for measurement of MHC class II expression in MSCs following stimulation with interferon (IFN)-γ was assessed. I...
Abo-Aziza FAM, Hendawy SHM, Namaky AHE, Ashry HM.The aim of this study was to investigate the early diagnosis of strongyle infection based on early changes in Th1 and Th2 cytokines beside the diagnostic accuracy values and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting profiles using prepared strongyles antigens. Methods: A total of 73 donkeys had a mean age of 4-32 years old were parasitologically examined for strongyle infection. The early changes in Th1 and Th2 cytokines were determined, and the diagnostic accuracy values and SDS-PAGE and western blotting profiles were performed using prepared st...
Jiménez-Aristizabal RF, López C, Álvarez ME, Giraldo C, Prades M, Carmona JU.To compare the temporal release (over three weeks) of tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-1 receptor antagonist (IL-1ra), platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta-1 (TGF-β1) from two platelet-rich fibrin (PRF) preparations from equine blood obtained at either 240g/8min or 416g/10min. Whole blood from 10 horses was used to obtain PRF clots by two different centrifugation protocols. After 1h of rest, PRF clots were deposited in wells with culture medium, which was changed at 6h, 24h and then every 48h to 21days. Cytokines and GFs...
Abdelhamid L, Hussein H, Ghanem M, Eissa N.Retinoic acid (RA), an active metabolite of vitamin A, has shown potential therapeutic immunomodulatory properties. Allogeneic mesenchymal stem cells (MSCs)-based therapy is an effective approach to induce tissue healing and regeneration in many equine orthopedic conditions. However, MSCs-based therapies induced inflammatory responses in vivo. This study aimed to: 1. Determine the effect of RA cell culture treatment on inflammatory responses of lipopolysaccharides (LPS)- and allogeneic MSCs-stimulated peripheral blood mononuclear cells (PBMCs). 2. Determine the effect of RA on stimulated MSCs ...
Kilborne AH, Hussein H, Bertone AL.OBJECTIVE To investigate effects of hyaluronic acid (HA) or HA combined with chondroitin sulfate (CS) and N-acetyl-d-glucosamine (NAG) by use of a lipopolysaccharide (LPS) in vitro method. SAMPLE Monolayer cultures of synovial cells from 4 adult horses. PROCEDURES Synovial cell cultures were untreated or treated with HA alone or HA-CS-NAG for 24 hours, subsequently unchallenged or challenge-exposed with 2 LPS concentrations (20 and 50 ng/mL) for 2 hours, and retreated with HA or HA-CS-NAG for another 24 hours. Cellular morphology of cultures was evaluated at 0, 24 (before LPS), 26 (after LPS),...
Mariella J, Castagnetti C, Prosperi A, Scagliarini A, Peli A.The purpose of this study is to investigate the presence of IL-4, IL-8, IL-13 and IFN-γ in equine colostrum and in foals' serum. Samples were obtained from 14 mares and their healthy foals. Soon after parturition, 10ml of colostrum was collected, filtered, centrifuged and frozen until assayed. Blood samples were obtained from each foal at birth (TO) and again after 24h (T24), after which they were frozen until assayed. Serum IgG was measured at 24h of age with an immunoturbidimetric quantitative method. Cytokine concentration was determined using commercially available ELISA tests. Statistica...
Niedźwiedź A, Borowicz H, Kubiak K, Nicpoń J, Skrzypczak P, Jaworski Z, Cegielski M, Nicpoń J.Recurrent airway obstruction (RAO) represents a serious health problem and is traditionally classified as an allergic disease, where contact with an antigen can induce clinical airway inflammation, bronchial hyper-responsiveness and reversible airway obstruction. Previous studies have demonstrated the presence of the Th2 response in the lungs of human patients with asthma and horses with heaves. These cells are involved in the production of cytokines which regulate the synthesis of immunoglobulins. 40 horses were evaluated: 30 horses with RAO and 10 healthy animals. The expression levels of in...
Frondoza CG, Fortuno LV, Grzanna MW, Ownby SL, Au AY, Rashmir-Raven AM.Objective Pro-inflammatory mediators such as prostaglandin E-2 (PGE2) play major roles in the pathogenesis of osteoarthritis (OA). Although current pharmacologic treatments reduce inflammation, their prolonged use is associated with deleterious side effects prompting the search for safer and effective alternative strategies. The present study evaluated whether chondrocyte production of PGE2 can be suppressed by the combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA). Design Chondrocytes from articular cartilage of equine joints were incubated for 24 hours with: (1) con...
Bonelli F, Meucci V, Divers TJ, Wagner B, Intorre L, Sgorbini M.Endotoxemia represents a significant clinical and economic problem for the equine industry. This study assesses the kinetics of soluble CD14 (sCD14), chemokine (CC motif) ligand 2 (CCL2), interleukin 10 (IL-10) and plasma procalcitonin (PCT) in healthy horses after the intravenous infusion of lipopolysaccharide (LPS). The aim was to contribute to the basic understanding of the equine species-specific kinetics of these molecules in response to LPS exposure, which could support further findings in clinical studies and identify valuable inflammatory biomarkers for equine practice. Eleven healthy ...
Barton AK, Pelli A, Rieger M, Gehlen H.Procalcitonin (PCT), a precursor protein of the hormone calcitonin, is a sensitive inflammatory marker in human medicine, which is primarily used for diagnosis of bacterial sepsis, but is also useful in diagnosis of exacerbation of asthma and COPD. In this study, PCT was evaluated as a potential biomarker for different chronic pneumopathies in the horse using an equine specific ELISA in comparison to established clinical markers and different interleukins. Sixty-four horses were classified as free of respiratory disease, recurrent airway obstruction (RAO), inflammatory airway disease (IAD) or ...
Barton AK, Gehlen H.Equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) represent a spectrum of chronic inflammatory disease of the airways in horses resembling human asthma in many aspects. Therefore, both are now described as severity grades of equine asthma. Increasing evidence in horses and humans suggests that local pulmonary inflammation is influenced by systemic inflammatory processes and the other way around. Inflammation, coagulation, and fibrinolysis as well as extracellular remodeling show close interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is comm...
Ziegler A, Gerber V, Marti E.Insect bite hypersensitivity (IBH) is an equine allergic dermatitis to Culicoides spp. antigens. Attempts at using allergen-specific immunotherapy (AIT) as a treatment for IBH have so far proven unsuccessful. Toll-like receptor (TLR) agonists can promote a shift in the immune response from the allergy-promoting T helper cell 2 (Th2) response towards a Th1 and/or regulatory response. The aim of this study was to evaluate two immunomodulatory TLR agonists in vitro as potential vaccine adjuvants for a more efficacious AIT in IBH. Peripheral blood mononuclear cells (PBMCs) from healthy and IBH-aff...
Evans CH, Chevalier X, Wehling P.Autologous conditioned serum was developed in the mid 1990s as an expeditious, practical, and relatively inexpensive means of generating the interleukin-1 receptor antagonist, a naturally occurring inhibitor of the cytokine interleukin-1. The latter is thought to be an important mediator of inflammation, pain, and tissue destruction in musculoskeletal conditions. ACS has been widely and successfully used in the local treatment of human and equine osteoarthritis and radicular compression; it has also shown promise in treating tendinopathies, muscle injuries, and tunnel widening after reconstruc...
Zucca E, Corsini E, Galbiati V, Lange-Consiglio A, Ferrucci F.Data obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. Recently, new therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. The aim of this study was to investigate the immunomodulatory effects of equine amniotic mesenchymal cell derivatives on lipopolysaccharide (LPS)-induced cytokine production in equine alveolar macrophages, which may be beneficial in lu...
Wise LM, Bodaan CJ, Mercer AA, Riley CB, Theoret CL.Wounds in horses often exhibit sustained inflammation and inefficient vascularization, leading to excessive fibrosis and clinical complications such as "proud flesh". Orf virus-derived proteins, vascular endothelial growth factor (VEGF)-E and interleukin (ovIL)-10, enhance angiogenesis and control inflammation and fibrosis in skin wounds of laboratory animals. Objective: The study aimed to determine if equine dermal cells respond to VEGF-E and ovIL-10. Equine dermal cells are expected to express VEGF and IL-10 receptors, so viral protein treatment is likely to alter cellular gene expression an...
Barussi FC, Bastos FZ, Leite LM, Fragoso FY, Senegaglia AC, Brofman PR, Nishiyama A, Pimpão CT, Michelotto PV.This research evaluated the effects of bone marrow-derived mononuclear cells (BMMCs) on the inflammatory process in the equine recurrent airway obstruction (RAO). Eight horses in RAO clinical score were divided into cell therapy group (Gcel) treated with a single intratracheal dose of BMMCs, and dexamethasone group (Gdex) treated with 21days of oral dexamethasone. The horses were clinically revaluated on days 7 and 21, together with cytological evaluation of the BALF, and detection of inflammatory markers (interleukins [IL]-10, -4, and -17, and interferon γ and α). There were decreases in re...
Simeonova GP, Krastev SZ, Simeonov RS.The pathogenic mechanism of equine recurrent uveitis (ERU) is still poorly defined and many variations between experimental animal models and spontaneous disease exist. Objective: The aim of our study was to investigate if Th17 cell-mediated response plays role in the pathogenesis of the used experimental model in horses and to reveal its pathological findings. Methods: Experimental uveitis was induced in 6 healthy horses. The concentrations of retinal autoantigen CRALBP and IL-17 were measured using ELISA in aqueous humor and vitreous body of the 12 inflamed eyes as well as in 12 control non-...
Rütten S, Schusser GF, Abraham G, Schrödl W.Horses are much predisposed and susceptible to excessive and acute inflammatory responses that cause the recruitment and stimulation of polymorphnuclear granulocytes (PMN) together with peripheral blood mononuclear cells (PBMC) and the release of cytokines. The aim of the study is to develop easy, quick, cheap and reproducible methods for measuring tumor necrosis factor alpha (TNF-α) and interleukin-1 receptor antagonist (IL-1Ra) in the equine whole blood cultures ex-vivo time- and concentration-dependently. Results: Horse whole blood diluted to 10, 20 and 50 % was stimulated with lipopolysa...
Gabner S, Hlavaty J, Velde K, Renner M, Jenner F, Egerbacher M.Osteoarthritis, a chronic and progressive degenerative joint disorder, ranks amongst the top five causes of disability. Given the high incidence, associated socioeconomic costs and the absence of effective disease-modifying therapies of osteoarthritis, cell-based treatments offer a promising new approach. Owing to their paracrine, differentiation and self-renewal abilities, mesenchymal stem cells (MSCs) have great potential for regenerative medicine, which might be further enhanced by targeted gene therapy. Hence, the development of systems allowing transgene expression, particularly when regu...
Siemieniuch MJ, Szóstek AZ, Gajos K, Kozdrowski R, Nowak M, Okuda K.Mares that fail to conceive or lose their embryos, without showing typical signs of clinical endometritis, should be suspected of subclinical endometritis (SE). In this study, the question was addressed: does SE fully activate selected mechanisms of innate immunity in mares? For this aim, expression of mRNAs for Toll-like Receptor 2 and 4 (TLR 2/4), interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF) was examined in control mares versus either mares suffering from chronic endometritis (ChE) or subacute suppurative endometritis (SSE). The concentrations of IL-1β, ...
Murcia RY, Vargas A, Lavoie JP.Glucocorticoids (GCs) are the most effective drugs for the treatment of human asthma. However, a subgroup of asthmatic patients with neutrophilic airway inflammation is insensitive to GCs. Interleukin-17 (IL-17), a cytokine upregulated in the airways of a subset of human asthmatic patients, contributes to the recruitment of neutrophils and induces a glucocorticoid resistance in human airway epithelial cells. We hypothesized that IL-17 similarly activates neutrophils and contributes to their persistence in the asthmatic airways in spite of glucocorticoid therapy. To determine whether IL-17 dire...
Hopster K, Jacobson B, Hopster-Iversen C, Rohn K, Kästner SBR.Inappropriate mechanical ventilation can lead to ventilator-induced lung injury (VILI). Aim of this study was to evaluate the effects of inhalation anaesthesia and ventilation with and without recruitment (RM) and PEEP titration on alveolar integrity in horses. Twenty-three horses were divided into 4 groups (group OLC ventilated with OLC, group IPPV ventilated with intermittent positive pressure ventilation, group NV non-ventilated, and group C non-anaesthetized control group). After sedation with xylazine and induction with diazepam and ketamine anaesthetized horses were under isoflurane anae...
Holcombe SJ, Jacobs CC, Cook VL, Gandy JC, Hauptman JG, Sordillo LM.Endotoxemia models are used to study mechanisms and treatments of early sepsis. Repeated endotoxin exposures induce periods of endotoxin tolerance, characterized by diminished proinflammatory responses to lipopolysaccharide (LPS) and modulated production of proinflammatory cytokines. Repeated measure designs using equine endotoxemia models are rarely performed, despite the advantages associated with reduced variability, because the altered responsiveness would confound study results and because the duration of equine endotoxin tolerance is unknown. We determined the interval of endotoxin toler...
Spaas JH, Gomiero C, Broeckx SY, Van Hecke L, Maccatrozzo L, Martens A, Martinello T, Patruno M.Several cytokines and growth factors play an essential role in skin regeneration and epithelial-like stem cells (EpSCs) have beneficial effects on wound healing in horses. However, there are no reports available on the expression of these growth factors and cytokines after EpSC therapy. Methods: Wounds of 6 cm(2) were induced in the gluteus region of 6 horses and treated with (i) autologous EpSCs, (ii) allogeneic EpSCs, (iii) vehicle treatment or (iv) untreated control. Real time polymerase chain reaction was performed on tissue biopsies taken 1 and 5 weeks after these treatments to evaluate...
Hussein H, Boyaka P, Dulin J, Bertone A.Cathepsin K (CatK) is an important enzyme regulating bone degradation and has been shown to contribute to the immune response. We have studied two inflammatory models in equine bone marrow nucleated cells (BMNCs); the LPS and the unmethylated CpG stimulation with the following objectives to: 1.determine whether CatK inhibition will alter the cytokine secretion by stimulated BMNCs; specifically IL-1β, IL-6, and TNF-α, and 2.determine the changes in BMNCs surface markers' expression and MHC II molecule under CatK inhibition. Cathepsin K inhibition promoted BMNCs viability and reduced cell apop...
Chen JW, Uboh CE, Robinson MA, Jiang Z, Soma LR.To evaluate plasma interleukin 6 (IL-6) concentration in Standardbred racehorses by means of a novel ELISA following validation of the assay for use with equine plasma samples. Methods: Plasma samples obtained from 25 Thoroughbreds for use in assay validation and from 319 Standardbred racehorses at rest 2 to 2.5 hours prior to warm-up and racing. Methods: A sandwich ELISA was developed with equine anti-IL-6 polyclonal antibody and the biotin-streptavidin chemical interaction to enhance sensitivity. The assay was validated for specificity, sensitivity, precision, and accuracy by use of both rec...
LaVigne EK, Jones AK, Londoño AS, Schauer AS, Patterson DF, Nadeau JA, Reed SA.Success as equine athletes requires proper muscle growth in young horses. Muscle hypertrophy occurs through protein synthesis and the contribution of muscle satellite cells, which can be stimulated or inhibited by cytokines and growth factors present during exercise and growth. The hypotheses of this study were that 1) the LM area in young horses would increase over 1 yr, and 2) specific cytokines and growth factors (IL-1β, IL-6, tumor necrosis factor [TNF]-α, IGF-I, and fibroblast growth factor [FGF]-2) would alter proliferation and differentiation of satellite cells isolated from young hor...
Korn A, Miller D, Dong L, Buckles EL, Wagner B, Ainsworth DM.Recurrent airway obstruction (RAO) is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest involvement of Inter...
Nielsen MK, Loynachan AT, Jacobsen S, Stewart JC, Reinemeyer CR, Horohov DW.Encysted cyathostomin larvae are ubiquitous in grazing horses. Arrested development occurs in this population and can lead to an accumulation of encysted larvae. Large numbers of tissue larvae place the horse at risk for developing larval cyathostominosis. This disease complex is caused by mass emergence of these larvae and is characterized by a generalized acute typhlocolitis and manifests itself as a profuse protein-losing watery diarrhea with a reported case-fatality rate of about 50%. Two anthelmintic formulations have a label claim for larvicidal therapy of these encysted stages; moxidect...
Martin EM, Messenger KM, Sheats MK, Jones SL.Pro-inflammatory cytokines including tumor necrosis factor α (TNFα), IL-1β, IL-6, and IL-8 are potent immune mediators that exacerbate multiple equine diseases such as sepsis and laminitis. Unfortunately, safe and effective cytokine-targeting therapies are lacking in horses; therefore, novel mechanisms of inhibiting cytokine production are critically needed. One potential mechanism for inhibiting cytokine synthesis is elevation of intracellular cyclic AMP (cAMP). In human leukocytes, intracellular cAMP production is induced by activation of E-prostanoid (EP) receptors 2 and 4. These recepto...
Cameron AD, Even KM, Linardi RL, Berglund AK, Schnabel LV, Engiles JB, Ortved KF.Joint injury can cause posttraumatic inflammation, which if severe enough can lead to posttraumatic osteoarthritis (PTOA), a progressive and debilitating condition. Posttraumatic inflammation is characterized by an influx of T lymphocytes and upregulation of inflammatory cytokines and degradative enzymes by activated chondrocytes and synoviocytes. Intra-articular bone marrow-derived mesenchymal stem cell (BM-MSC) injection for the treatment of osteoarthritis (OA) has been of interest due to the immunomodulatory properties of these cells. Interleukin (IL)-10, a potent immunomodulatory cytokine,...
Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR.Allogeneic and autologous bone marrow-derived mesenchymal stem cells (BMDMSCs) have been administered in equine joints for their anti-inflammatory effects. However, allogeneic BMDMSC offer multiple clinical and practical advantages. Therefore, it is important to determine the relative effectiveness of allogeneic vs autologous BMDMSCs. Objective: The objective of the study was to compare the inflamed joint response to autologous vs allogeneic BMDMSCs injections, and to determine if either treatment generated an anti-inflammatory effect. Methods: Randomised controlled study. Methods: Bone marrow...
Frondoza CG, Fortuno LV, Grzanna MW, Ownby SL, Au AY, Rashmir-Raven AM.Objective Pro-inflammatory mediators such as prostaglandin E-2 (PGE2) play major roles in the pathogenesis of osteoarthritis (OA). Although current pharmacologic treatments reduce inflammation, their prolonged use is associated with deleterious side effects prompting the search for safer and effective alternative strategies. The present study evaluated whether chondrocyte production of PGE2 can be suppressed by the combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA). Design Chondrocytes from articular cartilage of equine joints were incubated for 24 hours with: (1) con...
Horses affected by chronic piroplasmosis may develop poor performance and muscle atrophy. Here we investigate the pathological and immunopathological aspects of myopathy occurring in chronic equine piroplasmosis. The study included 16 horses serologically positive for equine piroplasms presenting with clinical signs and supporting serum biochemical evidence of a myopathy. Skeletal muscle was evaluated by histopathology, immunohistochemistry, indirect immunofluorescence, and molecular detection of piroplasms and inflammatory cytokines in skeletal muscle. Histologic lesions included muscle fiber...
Ainsworth DM, Matychak M, Reyner CL, Erb HN, Young JC.To examine effects of in vitro exposure to solutions of hay dust, lipopolysaccharide (LPS), or beta-glucan on chemokine and cell-surface receptor (CSR) gene expression in primary bronchial epithelial cell cultures (BECCs) established from healthy horses and horses with recurrent airway obstruction (RAO). Methods: BECCs established from bronchial biopsy specimens of 6 RAO-affected horses and 6 healthy horses. Methods: 5-day-old BECCs were treated with PBS solution, hay dust solutions, LPS, or beta-glucan for 6 or 24 hours. Gene expression of interleukin (IL)-8, chemokine (C-X-C motif) ligand 2 ...
Wagner B, Stokol T, Ainsworth DM.Transfer of maternal IgE antibodies to the neonate with the colostrum has been described in different mammalian species. Previous work in horses has shown that IgE bound to the surface of neonatal basophils is solely of maternal origin. However, the functional role of the maternal IgE transfer remained unclear. We hypothesized that maternal IgE mediates the onset of innate IL-4 production in equine neonatal basophils. Intracellular IL-4 production was measured in PBMC of newborn and older foals by flow cytometric analysis. A small population of IL-4(+) cells was observed in the peripheral bloo...
Dewachi O, Joubert P, Hamid Q, Lavoie JP.Heaves, a condition associated with airway neutrophilia, is believed to result from an allergic response to environmental dust particles. However, the contribution of neutrophils to the allergic response is poorly understood. It has been hypothesized that Th2-type cytokines can directly activate neutrophils to produce pro-inflammatory mediators. The present study focused on the presence of receptors for the Th2-type cytokines interleukin (IL)-5 and IL-9 on peripheral blood neutrophils of horses with heaves. Neutrophils were isolated from peripheral blood of horses with heaves (n=7), and normal...
Hamza E, Gerber V, Steinbach F, Marti E.Horses are particularly prone to allergic and autoimmune diseases, but little information about equine regulatory T cells (Treg) is currently available. The aim of this study therefore was to investigate the existence of CD4(+) Treg cells in horses, determine their suppressive function as well as their mechanism of action. Freshly isolated peripheral blood mononuclear cells (PBMC) from healthy horses were examined for CD4, CD25 and forkhead box P3 (FoxP3) expression. We show that equine FoxP3 is expressed constitutively by a population of CD4(+) CD25(+) T cells, mainly in the CD4(+) CD25(high)...
Ross-Jones TN, McIlwraith CW, Kisiday JD, Hess TM, Hansen DK, Black J.Dietary n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation has previously been shown to modify joint-related inflammation in several species, although information in the horse is lacking. We investigated whether dietary supplementation with n-3 LCPUFA would modify experimentally induced synovitis in horses. Twelve, skeletally mature, non-pregnant mares were randomly assigned to either a control diet (CONT) or an n-3 long-chain fatty acid-enriched treatment diet (N3FA) containing 40 g/day of n-3 LCPUFA for 91 days. Blood samples taken on days 0, 30, 60 and 90, and synovial flu...
Barton MH, Morris DD, Norton N, Prasse KW.Thirteen coagulation tests evaluating hemostatic and fibrinolytic indices and serum cytokine and plasma endotoxin concentrations were obtained in 34 foals with a positive sepsis score (septic group) and 46 age-matched healthy foals. Compared to healthy foals, the prothrombin, activated partial thromboplastin, and whole blood recalcification times were significantly longer in septic foals. The fibrinogen and fibrin degradation products concentrations, percent plasminogen, alpha-2 antiplasmin, and plasminogen activator inhibitor activities, and tumor necrosis factor and interleukin-6 activities ...
LeBlanc MM, Giguère S, Lester GD, Brauer K, Paccamonti DL.Ascending placentitis results in premature birth and high foal mortality. By understanding how placentitis induces premature delivery, it may be possible to develop diagnostic markers and to delay premature delivery pharmacologically, thereby decreasing perinatal foal mortality. Objective: To identify relationships between bacterial infection, inflammation and premature parturition in mares with experimentally induced placentitis. Methods: Experiment 1: Concentrations of allantoic fluid prostaglandins (PGs) F2alpha and E2 were measured in 8 mares after intracervical inoculation with Streptococ...
Pearson W, Orth MW, Lindinger MI.To evaluate inflammatory responses induced via intra-articular recombinant human interleukin (IL)-1beta treatment in horses receiving a dietary nutraceutical (DN; composed of mussel, shark cartilage, abalone, and Biota orientalis lipid extract) and assess the clinical effects of long-term DN administration. Methods: 22 healthy horses. Methods: 12 horses were fed 0, 15, 45, or 75 mg of DN (3 horses/treatment) daily for 84 days. General health and clinicopathologic variables were monitored at intervals. Ten other horses received 0 or 15 g of DN/d (5 horses/treatment) for 29 days (beginning day -...
Jacks S, Giguère S, Prescott JF.Rhodococcus equi is a facultative intracellular pathogen that causes pneumonia in foals but does not induce disease in adult horses. Virulence of R. equi depends on the presence of a large plasmid, which encodes a family of seven virulence-associated proteins (VapA and VapC to VapH). Eradication of R. equi from the lungs depends on gamma interferon (IFN-gamma) production by T lymphocytes. The objectives of the present study were to determine the relative in vivo expression of the vap genes of R. equi in the lungs of infected foals, to determine the recall response of bronchial lymph node (BLN)...
Wilson B, Novakofski KD, Donocoff RS, Liang YX, Fortier LA.Telomere length and telomerase activity are important indicators of cellular senescence and replicative ability. Loss of telomerase is associated with ageing and the development of osteoarthritis. Implantation of telomerase-positive cells, chondrocytes, or stem cells expressing a normal chondrocyte phenotype is desired for cartilage repair procedures. The objective of this study was to identify at what age chondrocytes and at what passage bone marrow-derived mesenchymal stem cells (MSCs) become senescent based on telomerase activity. The effect of osteogenic protein-1 (OP-1) or interleukin-1α...
Montgomery JB, Wichtel JJ, Wichtel MG, McNiven MA, McClure JT, Markham F, Horohov DW.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...
Plisak U, Szczepaniak J, Żmigrodzka M, Giercuszkiewicz-Hecold B, Witkowska-Piłaszewicz O.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...
Lanz S, Gerber V, Marti E, Rettmer H, Klukowska-Rötzler J, Gottstein B, Matthews JB, Pirie S, Hamza E.Equine recurrent airway obstruction (RAO) is an inflammatory, obstructive airway disease induced by exposure of susceptible horses to inhaled organic dust particles. The immunological process underlying RAO is still unclear. Previous studies have shown that RAO is linked to the Interleukin-4 receptor (IL-4R) gene in one Warmblood family (F1), but not in another (F2). It has also been shown that in F1, but not in F2, RAO is associated with resistance against parasites, suggesting that this association may have an immuno-genetic basis. Therefore, we hypothesized that the T helper (h)1/Th2/regula...
Heller MC, Drew CP, Jackson KA, Griffey S, Watson JL.Rhodococcus equi is a facultative intracellular bacterial pathogen of foals and immunocompromised humans that infects and proliferates within host macrophages and dendritic cells (DC). Indoleamine 2,3-dioxygenase (IDO), the initial enzyme in the tryptophan catabolism pathway, is upregulated in R. equi infected equine monocyte-derived DC and alveolar macrophages. Tryptophan requirement of R. equi for extracellular and intracellular growth was assessed. Growth of R. equi in minimal media did not require tryptophan and pharmacologic inhibition of IDO had no effect on intracellular proliferation o...
Ley C, Ekman S, Ronéus B, Eloranta ML.Cytokine production in synovial membranes (SM) and osteochondral fragments (OCF) may influence the development of equine osteoarthritis (OA). In this study, the presence of interleukin (IL)-6 and cytoplasmic and extracellular high mobility group box protein (HMGB)-1 in SM and osteochondral tissue from healthy and diseased equine joints was investigated by immunohistochemistry. Additionally, microscopic synovitis was graded. IL-6 was commonly found in SM cells and in chondrocytes in uncalcified cartilage of OCF, whereas little staining was detected in healthy cartilage. Cytoplasmic and/or extra...
Cohen ND, Bourquin JR, Bordin AI, Kuskie KR, Brake CN, Weaver KB, Liu M, Felippe MJ, Kogut MH.Neutrophils play an important role in protecting against infection. Foals have age-dependent deficiencies in neutrophil function that may contribute to their predisposition to infection. Thus, we investigated the ability of a CpG-ODN formulated with Emulsigen to modulate functional responses of neutrophils in neonatal foals. Eighteen foals were randomly assigned to receive either a CpG-ODN with Emulsigen (N = 9) or saline intramuscularly at ages 1 and 7 days. At ages 1, 3, 9, 14, and 28, blood was collected and neutrophils were isolated from each foal. Neutrophils were assessed for basal and R...
Müller JM, Wissemann J, Meli ML, Dasen G, Lutz H, Heinzerling L, Feige K.Whole blood pharmacokinetics of intratumourally injected naked plasmid DNA coding for equine Interleukin 12 (IL-12) was assessed as a means of in vivo gene transfer in the treatment of melanoma in grey horses. The expression of induced interferon gamma (IFN-g) was evaluated in order to determine the pharmacodynamic properties of in vivo gene transduction. Seven grey horses bearing melanoma were injected intratumourally with 250 µg naked plasmid DNA coding for IL-12. Peripheral blood and biopsies from the injection site were taken at 13 time points until day 14 post injection (p.i.). Samples w...
Figueiredo MD, Moore JN, Vandenplas ML, Sun WC, Murray TF.To evaluate proinflammatory effects of the second-generation synthetic lipid A analogue E5564 on equine whole blood and isolated monocytes and to determine the ability of E5564 to prevent LPS (lipopolysaccharide)-induced procoagulant activity (PCA); tumor necrosis factor (TNF)-alpha production; and mRNA expression of TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-10 by equine monocytes. Methods: Venous blood samples obtained from 19 healthy horses. Methods: Whole blood and monocytes were incubated with Escherichia coli O111:B4 LPS, E5564, or E5564 plus E coli O111:B4 LPS. Whole blood and cell...
El-Deeb W, Iacob O, Fayez M, Elgioushy M, Shawaf T, Ibrahim A.Habronemosis is a common parasitic disease of horses worldwide. In order to investigate how haptoglobin (Hp), serum amyloid A (SAA), oxidative stress markers, nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor (TNF- α), varies in cutaneous habronemosis, 30 horses with the clinical disease and 20 clinically healthy horses were included in the current study. The serum levels of Hp, SAA, and proinflammatory cytokines (IL-6 and TNF-α), NO, malondialdehyde (MDA), super oxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (TAC) were determined in horses before an...
Pusterla N, Wilson WD, Conrad PA, Barr BC, Ferraro GL, Daft BM, Leutenegger CM.This study was designed to determine the relative levels of gene transcription of selected pathogens and cytokines in the brain and spinal cord of 12 horses with equine protozoal myeloencephalitis (EPM), 11 with equine herpesvirus type 1 (EHV-1) myeloencephalopathy, and 12 healthy control horses by applying a real time pcr to the formalin-fixed and paraffin-embedded tissues. Total rna was extracted from each tissue, transcribed to complementary dna (cDNA) and assayed for Sarcocystis neurona, Neospora hughesi, EHV-1, equine GAPDH (housekeeping gene), tumour necrosis factor (TNF)-alpha, interfer...
Jackson KA, Stott JL, Horohov DW, Watson JL.The objectives of this study were to quantify the induction of equine CD23 transcripts in equine peripheral blood mononuclear cells (PBMCs) and pulmonary alveolar macrophages cultured with recombinant equine IL-4 (rEq IL-4). PBMCs were isolated from blood drawn from four healthy horses. Bronchoalveolar lavage (BAL) fluid was collected from three healthy horses and alveolar macrophages were purified using adherence to plastic for 120 min. PBMCs and alveolar macrophages were cultured using four different conditions: rEq IL-4 and LPS, LPS alone, rEq IL-4 alone and a media control. Total RNA was i...
Neil KM, Orth MW, Coussens PM, Chan PS, Caron JP.To determine whether glucosamine and chondroitin sulfate (CS) at concentrations approximating those achieved in plasma by oral administration would influence gene expression of selected mediators of osteoarthritis in cytokine-stimulated equine articular chondrocytes. Methods: Samples of grossly normal articular cartilage obtained from the metacarpophalangeal joint of 13 horses. Methods: Equine chondrocytes in pellet culture were stimulated with a subsaturating dose of recombinant equine interleukin (reIL)-1beta. Effects of prior incubation with glucosamine (2.5 to 10.0 microg/mL) and CS (5.0 t...
Kol A, Walker NJ, Galuppo LD, Clark KC, Buerchler S, Bernanke A, Borjesson DL.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...
Sponseller BA, de Macedo MM, Clark SK, Gallup JM, Jones DE.Foals are particularly vulnerable to infection by Rhodococcus equi during the first 2 weeks of life whereas mature horses are not. While an innate immunodeficiency likely accounts for this clinically relevant vulnerability, the factors that contribute to infection by R. equi have not been fully elucidated. In this study, we demonstrate that cells of the monocyte lineage, including monocytes, macrophages, and dendritic cells, that have been activated with LPS and IFN-gamma, respond with a statistically significant, greater amount of cytokine mRNA production of IL-10, IL-12p35, and IL-12p40 than...
Flaminio MJ, Nydam DV, Marquis H, Matychak MB, Giguère S.Susceptibility of foals to Rhodococcus equi pneumonia is exclusive to the first few months of life. The objective of this study was to investigate the immediate immunologic response of foal and adult horse antigen-presenting cells (APCs) upon infection with R. equi. We measured the activation of the antigen-presenting major histocompatibility complex (MHC) class II molecule, costimulatory molecules CD40 and CD86, the cytokine interleukin-12 (IL-12), and the transcriptional factor interferon regulatory factor 1 (IRF-1) in monocyte-derived macrophages (mMOs) and dendritic cells (mDCs) of adult h...
