The inflammatory response in horses is a complex physiological process that occurs when the immune system reacts to harmful stimuli such as pathogens, damaged cells, or irritants. This response is characterized by the activation of various immune cells, the release of signaling molecules, and the production of inflammatory mediators. In horses, the inflammatory response involves both innate and adaptive immune mechanisms, which work together to eliminate the source of harm and initiate tissue repair. Key components of the equine inflammatory response include cytokines, chemokines, and leukocytes, which coordinate the body's defense and healing processes. This page gathers peer-reviewed research studies and scholarly articles that explore the mechanisms, regulation, and implications of the inflammatory response in equine health and disease.
Honoré ML, Pihl TH, Busk-Anderson TM, Flintrup LL, Nielsen LN.D-dimer has value as a marker of thrombosis in critically ill horses and can provide additional information about prognosis. However, there are currently no equine species-specific d-dimer assays available, nor has there been any formal investigation of the applicability of human d-dimer assays in horses, so it is unknown, which assay performs best in this species. The aim of this study was therefore to evaluate and compare two human d-dimer assays for their applicability in horses. The study included four groups of horses: clinically healthy horses, horses with gastrointestinal (GI) disease a...
Taylor SD, Serpa PBS, Santos AP, Hart KA, Vaughn SA, Moore GE, Mukhopadhyay A, Page AE.A systemic and dysregulated immune response to infection contributes to morbidity and mortality associated with sepsis. Peripheral blood-derived mesenchymal stromal cells (PB-MSC) mitigate inflammation in animal models of sepsis. Allogeneic PB-MSC administered IV to horses is well-tolerated but therapeutic benefits are unknown. Objective: After IV lipopolysaccharide (LPS) infusion, horses treated with PB-MSC would have less severe clinical signs, clinicopathological abnormalities, inflammatory cytokine gene expression, and oxidative stress compared to controls administered a placebo. Methods: ...
Kingsley NB, Sandmeyer L, Bellone RR.Equine recurrent uveitis (ERU) is an ocular inflammatory disease that can be difficult to manage clinically. As such, it is the leading cause of bilateral blindness for horses. ERU is suspected to have a complex autoimmune etiology with both environmental and genetic risk factors contributing to onset and disease progression in some or all cases. Work in recent years has aimed at unraveling the primary triggers, such as infectious agents and inherited breed-specific risk factors, for disease onset, persistence, and progression. This review has aimed at encompassing those factors that have been...
Sanmartí J, Armengou L, Troya-Portillo L, Robles-Guirado JÁ, Bassols A, Ríos J, Jose-Cunilleras E.Magnesium disorders in horses with gastrointestinal disorders or systemic inflammatory response syndrome (SIRS) are scarcely characterized. The purpose of the study was to explore the association of magnesium disorders with diagnosis, SIRS and mortality in horses admitted to a referral equine hospital. In total, 75 sick horses were included in an observational prospective study and classified as: obstructive ( = 17), inflammatory ( = 10) and ischemic gastrointestinal disorders ( = 12), and other non-gastrointestinal systemic disorders ( = 36). All sick horses were also divided according to the...
Gilbertie JM, Schaer TP, Engiles JB, Seiler GS, Deddens BL, Schubert AG, Jacob ME, Stefanovski D, Ruthel G, Hickok NJ, Stowe DM, Frink A, Schnabel LV.The leading cause of treatment failure in Staphylococcus aureus infections is the development of biofilms. Biofilms are highly tolerant to conventional antibiotics which were developed against planktonic cells. Consequently, there is a lack of antibiofilm agents in the antibiotic development pipeline. To address this problem, we developed a platelet-rich plasma (PRP)-derived biologic, termed BIO-PLY (for the BIOactive fraction of Platelet-rich plasma LYsate) which has potent in vitro bactericidal activity against S. aureus synovial fluid free-floating biofilm aggregates. Additional in vitro st...
Garbin LC, Contino EK, Olver CS, Frisbie DD.Hemoderivatives such as autologous conditioned serum (ACS) and platelet-rich plasma (PRP) have been used as potential disease-modifying therapies in musculoskeletal disorders such as osteoarthritis (OA). These therapies are based on the delivery of multiple growth factors and anti-inflammatory cytokines that are known to participate in inflammatory processes. The variability of cytokine content due to the autologous nature of the product, the non-availability for immediate use and need for storage at low temperatures are limitations for its use in the field. An allogeneic freeze-dried conditio...
Hostetter JM, Uzal FA.Evaluation of gastrointestinal (GI) biopsies is a multistep process that includes reviewing an appropriate history, determining sample quality, and evaluating histologic sections. Selected diagnostic parameters that, in combination with intestinal histopathology, can be useful to localize disease to the intestinal tract in the horse include hypoproteinemia and hypoalbuminemia, ultrasound evidence of increased thickness of the small intestinal wall, and alterations in glucose or D-xylose absorption tests. Biopsies may be acquired either endoscopically, or via laparoscopy or standing flank incis...
McCoy AM, Secor EJ, Roady PJ, Gray SM, Klein J, Gutierrez-Nibeyro SD.Plantar osteochondral fragments (POF) are common but their effect on joint health of young Standardbreds in race training is largely unknown. Objective: Evaluate the inflammatory effects of POF in metatarsophalangeal joints of young Standardbreds as a step towards developing evidence-based recommendations for surgical removal. Methods: Cohort study. Methods: Forty-nine Standardbred horses (age 11-33 months) presented for surgical removal of POF from 56 metatarsophalangeal joints. Synovial tissue collected at arthroscopy was subjected to histopathology. IL-1β, TNF-α, and PGE-2 were measured ...
Airway inflammation and airway hyperresponsiveness (AHR) are pivotal characteristics of equine asthma. Lipopolysaccharide (LPS) may have a central role in modulating airway inflammation and dysfunction. Therefore, the aim of this study was to match the inflammatory and contractile profile in LPS-challenged equine isolated bronchi to identify molecular targets potentially suitable to counteract AHR in asthmatic horses. Equine isolated bronchi were incubated overnight with LPS (0.1-100 ng/ml). The contractile response to electrical field stimulation (EFS) and the levels of cytokines, chemokines...
Biondi V, Landi A, Pugliese M, Merola G, Passantino A.This study aimed to evaluate possible abnormalities in electrocardiographic findings, and changes in cardiac troponin I (cTnI) and inflammatory biomarkers (serum amyloid A (SAA) and C-reactive protein (CRP)) after inactivated herpesvirus vaccine administration. Eighteen healthy horses were included. All animals were vaccinated with Pneumoequine (Merial, France) according to the protocol provided by the manufacturer. They were evaluated 1 day before the first dose of vaccination (D0), and 7 days (D1) and 14 days (D2) afterwards. At D0, D1, and D2, a blood sample was taken for the evaluation of ...
Jasiński T, Zdrojkowski Ł, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Domino M.Endometritis is an important issue decreasing mares' fertility. In the case of endometritis, both inflammatory cells infiltration and proinflammatory molecules production are regulated by various cellular and gene regulatory mechanisms, including the nuclear factor-κB (NF-κB)-dependent pathway. NF-κB-signalling pathway has been recently studied in the equine endometrium in the context of endometrosis. Thus, this study aimed to determine gene transcription of NF-κB subunits (RelA; NF-κB1; NF-κB2), proinflammatory molecules (MCP-1; IL-6) and hyaluronan synthases (HAS 1; HAS 2; HAS 3) in en...
Niroomandi E, Maleki S, Abdollahpour G, Zakian A, Ahmadvand H.Leptospirosis is one of the important zoonotic bacterial diseases with a worldwide distribution that is often subclinical. We aimed to investigate the oxidant/antioxidant balance and acute-phase response in naturally infected horses and cattle with Leptospira interrogans. A total of 600 serum samples from horses and cattle were examined for L. interrogans antibodies using the microscopic agglutination test to determine anti-Leptospira IgG antibodies against a panel of eight important Leptospira antigens in Iran. Then, serum total antioxidant capacity, catalase, glutathione peroxidase, and malo...
Theuerkauf K, Obach-Schröck C, Staszyk C, Moritz A, Roscher KA.In humans, activated platelets contribute to sepsis complications and to multiple organ failure. In our prospective analytical study of cases of the equine systemic inflammatory response syndrome (SIRS), we adapted a standard human protocol for the measurement of activated platelets and platelet-leukocyte aggregates (PLAs) in equine platelet-leukocyte-rich plasma (PLRP) by flow cytometry, and we investigated the hypothesis that activated platelets and PLAs are increased in clinical cases of SIRS. We included 17 adult horses and ponies fulfilling at least 2 SIRS criteria, and 10 healthy equids ...
Roth P, Stanley J, Chamoun-Emanuelli A, Whitfield-Cargile C, Coleman M.To compare the inflammatory response of murine macrophages exposed to the enteric microbiome of obese horses versus nonobese horses. Methods: Fecal samples from 12 obese horses (body condition score ≥ 7/9) and 12 nonobese horses (body condition score 4 to 5/9) with similar dietary management. Methods: Fecal supernatant was prepared from frozen fecal samples. RAW 264.7 macrophage cells were exposed to the fecal extract. Inflammatory cytokine (interleukin-1β, tumor necrosis factor-α, and interleukin-6) gene expression was quantified via real-time quantitative reverse transcription PCR assay,...
Kozhakhmetov S, Babenko D, Kozhakhmetova S, Tuyakova A, Nurgaziyev M, Nurgozhina A, Muhanbetganov N, Chulenbayeva L, Sergazy S, Gulyayev A, Aljofan M....Ulcerative colitis is an inflammatory bowel disease that forms ulcerations in the mucous membrane of the colon and rectum, in which gut microbiota plays a pivotal role in its pathogenesis. Agents modulating microbial dysbiosis caused by colitis can help in the remission of this disease. The current study describes the potential therapeutic effects of active metabolites from Lactobacillus rhamnosus and mare's milk which have potential therapeutic values on the intestinal microbiota and proinflammatory cytokines. The analysis of the V1-V3 16S rDNA site revealed significant changes in the intesti...
Adamič N, Prpar Mihevc S, Blagus R, Kramarič P, Krapež U, Majdič G, Viel L, Hoffman AM, Bienzle D, Vengust M.Severe equine asthma (SEA) is a common chronic respiratory disease and a significant health and well-being problem in horses. Current therapeutic strategies improve pulmonary function and clinical signs in some horses, but in the long-term, return to full athletic function appears to be rare. The aim of this study was to assess the safety and the effect of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) on pulmonary inflammatory and clinical parameters in horses with SEA. This was a randomized controlled trial. Twenty adult horses diagnosed with SEA were random...
Radcliffe RM, Hill JA, Liu SY, Cook VL, Hurcombe SDA, Divers TJ.Abdominocentesis is commonly used to evaluate the abdominal cavity of the horse. This technique provides valuable diagnostic information as well as the means to monitor patients with abdominal diseases being managed medically and to determine their need for surgical management. Complications are uncommon and include trauma to the gastrointestinal tract or spleen, septic peritonitis, or abdominal wall infection. Methods: This review describes the indications, utility, patient preparation, and instructions for performing abdominocentesis as well as possible complications reported in horses. Step...
Beck AA, Paz LB, Frank MI, Engelmann AM, Krause A, Côrte FD.Botulinum toxin type A (BoNT-A) is a promising alternative for patients suffering from chronic joint pain. The aim of this study was to investigate whether a single injection of BoNT-A would produce adverse effects on clinical parameters and synovial parameters as well as lameness. One randomly selected radiocarpal joint was treated with 50 U of BoNT-A in eight horses, and the contralateral joint received saline solution. All horses received injections at day 0 and were re-evaluated twice daily for 7 days for heart rate (HR), respiratory rate (RR), rectal temperature (RT), mucous membrane colo...
Morrell JM, Rocha A.One of the most commonly encountered challenges in equine breeding is endometritis, which can be difficult to resolve and causes considerable economic losses to the industry. It is a multifactorial condition, developing as an exaggerated form of the normal physiological response to breeding. Seminal plasma proteins, spermatozoa, bacteria and debris initiate an inflammatory response; the resulting fluid and neutrophils are then cleared from the uterus along with the debris. However, in some mares, the response is prolonged or exaggerated, with much fluid formation and neutrophil infiltration le...
Fuentes-Romero B, Muñoz-Prieto A, Cerón JJ, Martín-Cuervo M, Iglesias-García M, Aguilera-Tejero E, Díez-Castro E.Obesity and its associated complications, such as metabolic syndrome, are an increasing problem in both humans and horses in the developed world. The expression patterns of resistin differ considerably between species. In rodents, resistin is expressed by adipocytes and is related to obesity and ID. In humans, resistin is predominantly produced by inflammatory cells, and resistin concentrations do not reflect the degree of obesity, although they may predict cardiovascular outcomes. The aim of this study was to investigate the usefulness of resistin and its relationship with ID and selected ind...
Lee GKC, Beeler-Marfisi J, Viel L, Piché É, Kang H, Sears W, Bienzle D.Horses with severe equine asthma (SEA), also known as heaves and recurrent airway obstruction, have persistent neutrophilic inflammation of the lower airways. Cytologic evaluation of bronchoalveolar lavage (BAL) fluid is commonly used to confirm the clinical diagnosis of SEA. However, the utility of microscopic assessment of bronchial brushings, endobronchial biopsies, and immunohistochemical detection of disease-associated biomarkers for the diagnosis of SEA remain poorly characterized. Salivary scavenger and agglutinin (SALSA) has anti-inflammatory properties and downregulated gene expressio...
Rozario C, Martínez-Sobrido L, McSorley HJ, Chauché C.Influenza A viruses (IAVs) are important respiratory pathogens of horses and humans. Infected individuals develop typical respiratory disorders associated with the death of airway epithelial cells (AECs) in infected areas. Virulence and risk of secondary bacterial infections vary among IAV strains. The IAV non-structural proteins, NS1, PB1-F2, and PA-X are important virulence factors controlling AEC death and host immune responses to viral and bacterial infection. Polymorphism in these proteins impacts their function. Evidence from human and mouse studies indicates that upon IAV infection, the...
Colombo I, Mislei B, Mari G, Iacono E, Merlo B.Many mares are susceptible to persistent mating-induced endometritis (PMIE), an important cause of reduced fertility. Platelet lysate (PL) derives from freeze-thawing platelets after concentration, so that growth factors are released from the platelets. Among the advantages of PL compared to platelet-rich plasma (PRP), it can be frozen stored and allogenic use for PL might also be conceivable. Platelet-rich plasma beneficially reduced inflammatory response in PMIE mares when administered 24 h pre- or 4 h post-AI. The aim of this study was to test the effect of PL on inflammatory uterine resp...
Bazzano M, Bonfili L, Eleuteri AM, Serri E, Scollo C, Yaosen Y, Tesei B, Laus F.A proper knowledge of biochemical parameters and inflammatory markers like serum amyloid A (SAA) is crucial in the monitoring of the first post-partum period in equids. Since no information is available on SAA for donkeys at this stage, 50 animals including jennies (n.10) and newborn foals (n.10) within 48 hr from foaling, and jennies (n.10) and foals (n.20) after 30 days from parturition were enrolled in the study to assess routine biochemical profile including SAA. Jennies showed higher alkaline phosphatase and lower bilirubins and cholesterol at 30 days of lactation compared to post-part...
Olave CJ, Ivester KM, Couëtil LL, Franco-Marmolejo J, Mukhopadhyay A, Robinson JP, Park JH.To investigate the role of omega-3 polyunsaturated fatty acids (Ω-3)-derived proresolving lipid mediators (PRLM) in the resolution of mild airway inflammation in horses. Methods: 20 horses with mild airway inflammation. Methods: Horses previously eating hay were fed hay pellets (low Ω-3 content; n = 10) or haylage (high Ω-3 content; 9) for 6 weeks. Dust exposure was measured in the breathing zone with a real-time particulate monitor. Bronchoalveolar lavage (BAL) was performed at baseline, week 3, and week 6. The effect of PRLM on neutrophil apoptosis and efferocytosis was examined in vitro....
Suagee-Bedore J, Shost N, Miller C, Grado L, Bechelli J.Older horses and those prone to obesity may be at a higher risk for inflammation than younger and leaner counterparts. Previous research indicated a postprandial elevation in plasma concentrations of interleukin-1β (IL-1β), a pro-inflammatory cytokine, after consuming 1.2 g of non-structural carbohydrates/kilogram of body weight. However, these studies utilized horses of mixed age and body condition. The current study evaluated post-prandial IL-1β concentrations in horses specifically comparing lean to over-conditioned and middle aged to older. Our results suggest that at least two weeks of...
Leise BS, Fugler LA.Sepsis or systemic inflammatory response syndrome (SIRS) -associated laminitis is a sequela to primary inflammatory conditions (eg, colitis, ischemic intestinal injury, pneumonia, metritis) and results from a dysregulated systemic inflammatory response that ultimately affects the digital lamellae. Local chemokine production, leukocyte migration, and proinflammatory mediator production occur within the lamellae that can lead to catastrophic lamellar failure. Controlling the primary disease, providing supportive care and anti-inflammatory therapy, applying digital cryotherapy, and providing mech...
Estrada McDermott J, Pezzanite L, Goodrich L, Santangelo K, Chow L, Dow S, Wheat W.Osteoarthritis (OA) is a common condition with diverse etiologies, affecting horses, humans, and companion animals. Importantly, OA is not a single disease, but rather a disease process initiated by different events, including acute trauma, irregular or repetitive overload of articular structures, and spontaneous development with aging. Our understanding of the pathogenesis of OA is still evolving, and OA is increasingly considered a multifactorial disease in which the innate immune system plays a key role in regulating and perpetuating low-grade inflammation, resulting in sustained cartilage ...
Villagrán CC, Vogt D, Gupta A, Fernández EA.A 3-year-old Quarter Horse gelding was evaluated for chronic weight loss, diarrhea, and pruritus. Physical examination revealed several ulcerative lesions on the skin and mucosal membranes. Diagnostic imaging findings were consistent with enteritis, typhlitis, and colitis. Multisystemic eosinophilic epitheliotropic disease (MEED) was diagnosed upon necropsy. This disease may be considered a form of equine inflammatory bowel disease complex which can be challenging to diagnose, requiring histological assessment, and in some cases, the use of immunohistochemical markers. Key clinical message: Mu...
Hay AN, Wagner B, Leeth CM, LeRoith T, Cecere TE, Lahmers KK, Andrews FM, Werre SR, Johnson AL, Clark CK, Pusterla N, Reed SM, Lindsay DS, Taylor S....Equine protozoal myeloencephalitis (EPM) is a debilitating neurologic disease affecting horses across the Americas. Gaps in understanding the inflammatory immune response in EPM-affected horses create difficulties with diagnosis and treatment, subsequently negatively impacting the prognosis of affected horses. The purpose of the current study was to evaluate circulating levels of the inflammatory immune marker soluble CD14 (sCD14), in horses with EPM (n = 7) and determine if they differed from healthy neurologically normal horses (n = 6). Paired sera and cerebrospinal fluid (CSF) samples were ...
Hraha TH, Doremus KM, McIlwraith CW, Frisbie DD.Osteoarthritis (OA) is one of the most prevalent and debilitating conditions affecting the horse. Autologous conditioned serum (ACS), commercially available as IRAP and IRAP II, is a recently developed treatment for OA in which plasma is prepared from venous blood by incubation with glass beads for 24 h. This product has been shown to increase anti-inflammatory cytokines and growth factors in human blood. However, data for equine ACS preparations are lacking. Objective: To characterise the protein profiles produced by commercially available ACS systems in equine blood. Methods: Blood was dra...
Pollock PJ, Prendergast M, Schumacher J, Bellenger CR.The serum concentrations of serum amyloid A, haptoglobin and fibrinogen were measured in a group of horses before and at intervals after elective and non-elective surgery, and in a control group of normal horses. There was a significant, rapid and repeatable increase in the concentration of serum amyloid A in response to both elective and non-elective surgery. In the control horses its serum concentration was within the normal range, from 0 to 0.2 microg/ml. Twenty-four hours after elective surgery its mean peak concentration was 16.4 microg/ml, and after non-elective surgery it was 27.3 micro...
Register TC, Cann JA, Kaplan JR, Williams JK, Adams MR, Morgan TM, Anthony MS, Blair RM, Wagner JD, Clarkson TB.The effects of dietary soy isoflavones (IF) and conjugated equine estrogens (CEE) on circulating inflammatory markers were determined at the end of a 3-yr study of ovariectomized monkeys consuming a moderately atherogenic diet. Treatments were: 1) control, receiving alcohol-extracted soy-protein-based diet with low IF content (comparable to approximately 5 mg/d); 2) CEE, added to the control diet at a dose comparable to 0.625 mg/d; and 3) IF, consumed as a part of unextracted soy protein isolate at a dose comparable to 129 mg/d. Serum soluble vascular cell adhesion molecule-1 (sVCAM-1) was red...
Menarim BC, Gillis KH, Oliver A, Ngo Y, Werre SR, Barrett SH, Rodgerson DH, Dahlgren LA.Synovitis is a major component of osteoarthritis and is driven primarily by macrophages. Synovial macrophages are crucial for joint homeostasis (M2-like phenotype), but induce inflammation (M1-like) when regulatory functions become overwhelmed. Macrophage phenotypes in synovium from osteoarthritic and healthy joints are poorly characterized; however, comparative knowledge of their phenotypes during health and disease is paramount for developing targeted treatments. This study compared patterns of macrophage activation in healthy and osteoarthritic equine synovium and correlated histology with ...
Liburt NR, Adams AA, Betancourt A, Horohov DW, McKeever KH.Studies have demonstrated increases in mRNA expression for inflammatory cytokines following exercise in horses and have suggested those markers of inflammation may play a role in delayed onset muscle soreness. However, measurement of mRNA expression in white blood cells is an indirect method. No studies to date have documented the cytokine response to exercise directly in muscle in horses. Objective: This study tested the hypothesis that exercise increases cytokine markers of inflammation in blood and muscle. Methods: Blood and muscle biopsies were obtained from 4 healthy, unfit Standardbred m...
Mullen KR, Yasuda K, Divers TJ, Weese JS.While certainly not a novel concept, faecal microbiota transplant (FMT) has recently garnered renewed interest in veterinary medicine due to its remarkable success in treating recurrent Clostridium difficile infection (CDI) in man. There is a dearth of information on indications and efficacy of FMT for the treatment of gastrointestinal disorders in the horse; however, based on evidence in man and other veterinary species, and anecdotal reports in horses, FMT may be a useful treatment for selected cases of acute and chronic diarrhoea and inflammatory bowel disease (IBD) in the horse. In the abs...
Lavoie-Lamoureux A, Leclere M, Lemos K, Wagner B, Lavoie JP.Systemic inflammation in horses with heaves is poorly characterized. Objective: To assess acute phase proteins (APP) and inflammatory cytokine profiles in serum of healthy horses and horses with heaves. Methods: Six healthy horses and 6 heaves-affected horses belonging to the University of Montreal. Methods: Prospective, observational study. Healthy and heaves-affected control horses were exposed to a 30-day natural challenge with hay and straw to induce clinical exacerbation of heaves. Serum samples were obtained by venipuncture before (T0) as well as after 7 (T7) and 30 days (T30) of stablin...
Duncan JL, Pirie HM.The clinical signs, pathology and clinical pathology associated with single experimental infections of Strongylus vulgaris in worm-free pony foals are described. The major clinical signs which became apparent in the infected foals during the first three weeks were pyrexia, anorexia, dullness and abdominal pain. Within the first two weeks of infection lesions were confined to the intestine and terminal branches of the intestinal arteries and consisted of mucosal, submucosal and serosal haemorrhage together with arteritis of submucosal and serosal arteries and also a marked inflammatory reaction...
Dauvillier J, Ter Woort F, van Erck-Westergren E.Fungi contribute to the inflammatory response of lungs in horses with recurrent airway obstruction and in some forms of asthma in humans. The role of fungi in inflammatory airway disease (IAD) has not been assessed. Objective: Evaluate the prevalence of fungi in the respiratory samples of horses diagnosed with IAD, describe clinical signs associated with the presence of fungi in respiratory samples, and assess the risk factors associated with IAD and with the presence of fungi in the airways. Methods: Seven-hundred thirty-one active horses referred to a specialized ambulatory practice for sign...
Bertoni L, Branly T, Jacquet S, Desancé M, Desquilbet L, Rivory P, Hartmann DJ, Denoix JM, Audigié F, Galéra P, Demoor M.Osteoarthritis is a significant and costly cause of pain for both humans and horses. The horse has been identified as a suitable model for human osteoarthritis. Regenerative therapy with allogeneic mesenchymal stem cells (MSCs) is a promising treatment, but the safety of this procedure continues to be debated. The aim of this study is to evaluate the safety of intra-articular injections of allogeneic MSCs on healthy joints by comparing two different dosages and two different tissue sources, namely, bone marrow and umbilical cord blood, with a placebo treatment on the same individuals. We also ...
Bureau F, Bonizzi G, Kirschvink N, Delhalle S, Desmecht D, Merville MP, Bours V, Lekeux P.Asthma is a chronic inflammatory disease of the airways, in which many inflammatory genes are overexpressed. Transcription factor, nuclear factor-kappaB (NF-kappaB), which is thought to control the transcriptional initiation of inflammatory genes, has been poorly investigated in asthma. In the present report, bronchial cells (BCs), recovered by bronchial brushing in healthy and heaves-affected horses (i.e., an animal model of asthma), were assessed for NF-kappaB activity. Small amounts of active NF-kappaB were present in BCs of healthy horses, whereas high levels of NF-kappaB activity was foun...
Hultén C, Grönlund U, Hirvonen J, Tulamo RM, Suominen MM, Marhaug G, Forsberg M.Despite the importance of noninfectious joint diseases in equine medicine, little is known about the acute phase response which may be elicited if the local inflammatory process of noninfectious arthritis is sufficiently strong, Therefore the aim of this study was to monitor the systemic inflammatory response during experimentally-induced noninfectious arthritis by studying the dynamics in serum of the acute phase proteins serum amyloid A (SAA), haptoglobin, fibrinogen and alpha2-globulins. Twenty-four Standardbred horses, age 3-7 years, found healthy on thorough clinical, radiological, haemat...
Williams LB, Koenig JB, Black B, Gibson TW, Sharif S, Koch TG.Improvement has been reported following intra-articular (i.a.) injection of mesenchymal stromal cells (MSCs) in several species. These observations have led to the use of i.a. MSCs in equine practice with little understanding of the mechanisms by which perceived improvement occurs. Objective: To evaluate the effect of i.a. allogeneic umbilical cord blood (CB-) derived MSCs using a lipopolysaccharide (LPS) induced synovitis model. We hypothesised that i.a. CB-MSCs would reduce the inflammatory response associated with LPS injection. Methods: Randomised, blinded experimental study. Methods: Feas...
Padalino B, Raidal SL, Carter N, Celi P, Muscatello G, Jeffcott L, de Silva K.Horses are transported frequently and often over long distances. Transportation may represent a physiological stressor with consequential health and welfare implications. This study reports the effects of a long distance journey on immunological, clinical, haematological, inflammatory and oxidative parameters in an Experimental Group (EG) of ten horses, comparing them with six horses of similar age and breed used as a non-transported Control Group (CG). Clinical examination and blood sampling were performed twice on all horses: immediately after unloading for the EG, and at rest on the same da...
De Schauwer C, Van de Walle GR, Van Soom A, Meyer E.In the past decade, mesenchymal stem cells (MSC) have received much attention in equine veterinary medicine. The first therapeutic use of equine MSC was reported in 2003. Since then, the clinical application of MSC has been exploding with thousands of horses now treated worldwide. At present, MSC are mainly used in veterinary medicine to treat musculoskeletal diseases based on their ability to differentiate into various tissues of mesodermal origin. This is in marked contrast to human medicine, where MSC therapies are primarily focused on immune-mediated, inflammatory, and ischemic diseases. I...
Moore JN, Vandenplas ML.Some veterinarians describe particularly sick horses or neonatal foals as being endotoxemic, whereas others refer to the same animals as having the systemic inflammatory response syndrome. This article reviews the basis for the use of each of these terms in equine practice, and highlights the mechanisms underlying the response of the horse's innate immune system to key structural components of the microorganisms that initiate these conditions, including how some of those responses differ from other species. Current approaches used to treat horses with these conditions are summarized, and cauti...
Linardi RL, Dodson ME, Moss KL, King WJ, Ortved KF.Cartilage injury occurs commonly in equine athletes, often precipitating posttraumatic osteoarthritis (PTOA). Orthobiologics such as autologous conditioned serum (ACS) and autologous protein solution (APS) may be useful in decreasing posttraumatic inflammation, thereby preventing PTOA. The objective of this study was to quantify cytokine concentrations in ACS and APS and evaluate the protective effects of ACS and APS on inflamed chondrocytes cultured . We hypothesized that the combination of platelet-derived growth factors (PDGF) and anti-inflammatory cytokines present in APS would be superior...
Hauck SM, Schoeffmann S, Amann B, Stangassinger M, Gerhards H, Ueffing M, Deeg CA.Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye. Although retinal-autoantigen specific T-helper 1 cells have been demonstrated to trigger disease progression and relapses, the molecular processes leading to retinal degeneration and consequent blindness remain unknown. To elucidate such processes, we studied changes in the total retinal proteome of ERU-diseased horses compared to healthy controls. Severe changes in the retinal proteome were found for several markers for blood-retinal barrier breakdown and whose emergence depended upon disease seve...
Cokelaere SM, Plomp SGM, de Boef E, de Leeuw M, Bool S, van de Lest CHA, van Weeren PR, Korthagen NM.Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple L...
Fernandez NJ, Hecker KG, Gilroy CV, Warren AL, Léguillette R.Reliable enumeration of mast cells and eosinophils in equine bronchoalveolar lavage (BAL) fluid is important because small increases in the percentages of these cells support the clinical diagnosis of inflammatory airway disease (IAD). Increases in BAL neutrophils also occur with IAD but are not specific due to overlap between IAD and recurrent airway obstruction (RAO). Objective: The objectives of this study were to evaluate the reliability of a standard 400-cell leukocyte differential count and an alternate method evaluating 5 microscopic fields at 500× magnification in equine BAL fluid cyt...
Andersen SA, Petersen HH, Ersbøll AK, Falk-Rønne J, Jacobsen S.European and American guidelines for vaccination against tetanus and influenza in horses recommend annual and annual/semi-annual vaccinations, respectively, against the two pathogens. Too-frequent vaccination may, however, have adverse effects, among other things because an inflammatory response is elicited with subsequent alterations in homeostasis. The objective of the study was to compare the acute phase response (APR) in 10 horses following administration of two different types of vaccines, namely, an inactivated Immune Stimulating COMplex (ISCOM) vaccine and a live recombinant vector vacc...
Morris DD.Endotoxemia remains the leading cause of death in horses, being intimately involved in the pathogenesis of gastrointestinal disorders that cause colic and neonatal foal septicemia. Endotoxins, normally present within the bowel, gain access to the blood across damaged intestinal mucosa, or endotoxemia occurs when gram negative organisms proliferate in tissues. Endotoxins are removed from the circulation by the mononuclear phagocyte system, and the response of mononuclear phagocytes to these lipopolysaccharides (LPS) play an important role in determining the severity of clinical disease. Macroph...
Deeg CA, Ehrenhofer M, Thurau SR, Reese S, Wildner G, Kaspers B.Equine recurrent uveitis (ERU) is the most serious eye disease in horses worldwide. Despite the fact that ERU is generally considered to be immune mediated, a detailed description of the histopathology of the posterior part of ERU eyes is lacking. Here, we examined sections of paraffin-embedded eyes using histological and immunhistological methods. Twenty seven eyes of 20 horses with ERU and 30 eyes of 15 healthy control horses were included in this study. We could consistently demonstrate an involvement of the retina and the choroid in all examined eyes of horses with spontaneous ERU. In eyes...
Müller J, Feige K, Wunderlin P, Hödl A, Meli ML, Seltenhammer M, Grest P, Nicolson L, Schelling C, Heinzerling LM.Melanoma is a disease with high incidence in gray horses and has limited therapeutic options in metastatic disease. Gene therapy has shown some success in animal models and human patients. A randomized double-blind, placebo-controlled study was conducted to investigate 2 treatment options using cytokine-encoding plasmid DNA in horses with metastatic melanoma to induce immunologic antitumor effects. Adult gray horses with spontaneously occurring metastatic melanoma (n=26) were included in the study. Treatment of 26 gray horses with metastatic melanoma consisted of interleukin-18-encoding plasmi...
Adams AA, Breathnach CC, Katepalli MP, Kohler K, Horohov DW.A number of model systems have been employed to investigate age-associated changes in immune function. The purpose of the current study was to characterize senescent T cells and to investigate the inflamm-aging phenomenon both in vitro and in vivo using the old horse as a model. We examined whether decreased T cell proliferation induced by Con A is caused by increased apoptosis. We also utilized intracellular CFSE to analyze changes within each round of cell proliferation, in particular cytokine production. Intracellular staining with flow cytometry, RT-PCR, and ELISA were used to measure pro-...
Robinson NE, Karmaus W, Holcombe SJ, Carr EA, Derksen FJ.Although subclinical airway inflammation is thought to be common in horses, there is little information on its prevalence and none on risk factors. Objective: To determine the prevalence and risk factors for an increased number of inflammatory cells and for mucus accumulation in the trachea of pleasure horses. Methods: Horses (n = 266) in stables (n = 21) in Michigan were examined endoscopically, once in winter and once in summer 2004. Visible tracheal mucoid secretions were graded 0-5 and inflammatory cell numbers counted in a tracheal lavage sample. Information collected about each horse inc...
Richard EA, Depecker M, Defontis M, Leleu C, Fortier G, Pitel PH, Couroucé-Malblanc A.Multiple cytological patterns occur in bronchoalveolar lavage fluid (BALF) of horses with inflammatory airway disease (IAD). Only few data on BALF cytokine profiles are available for horses with IAD, and are limited to mRNA expression. Objective: Cytological profiles of IAD are associated with different BALF immunological pathways. To investigate BALF cytokine concentrations in a large number of horses with neutrophilic IAD. Methods: One hundred and thirty-eight client-owned Standardbred racehorses in active training. Methods: Prospective observational study. BALF samples were obtained from le...
Lavoie-Lamoureux A, Moran K, Beauchamp G, Mauel S, Steinbach F, Lefebvre-Lavoie J, Martin JG, Lavoie JP.Neutrophils are potent contributors to the lung pathophysiological changes occurring in allergic airway inflammation, which typically involve T helper type 2 (Th2) cytokine overexpression. We have previously reported that equine pulmonary endothelial cells are activated by the Th2 cytokine IL-4 and express chemotactic factors for neutrophils after stimulation. We have further explored the possible mechanisms linking Th2-driven inflammation and neutrophilia by studying the effects of recombinant equine IL-4, a prototypical Th2 cytokine, on peripheral blood neutrophils (PBN) isolated from normal...
Adams AA, Katepalli MP, Kohler K, Reedy SE, Stilz JP, Vick MM, Fitzgerald BP, Lawrence LM, Horohov DW.Advanced age is associated with a low-grade, systemic inflammatory response characterized by increased inflammatory cytokine production both in vitro and in vivo, termed inflamm-aging. It is also known that increased white adipose tissue, associated with obesity, leads to increased production of inflammatory cytokines. To date, it is unknown whether increased adiposity contributes to the age-related increased inflammatory status. Here we show that peripheral blood mononuclear cells (PBMC) from old horses compared to young horses have increased inflammatory cytokine production; moreover, fat ol...
Allen KJ, Tremaine WH, Franklin SH.Inflammatory airway disease (IAD) is thought to be an important cause of poor performance in young Thoroughbred racehorses. However, little study has been made of IAD in older National Hunt (NH) horses. Objective: To determine the prevalence of IAD in NH racehorses referred for investigation of poor athletic performance and identify some of the risk factors that may be associated with IAD in this group of horses. Methods: Tracheal mucus was graded, and tracheal wash (TW) and bronchoalveolar lavage (BAL) performed after treadmill exercise in 91 NH horses referred to the University of Bristol. C...
