Tumor Necrosis Factor (TNF) is a cytokine involved in the inflammatory response in horses. It is produced by various cells, including macrophages, in reaction to infection, injury, or immune challenges. TNF plays a role in regulating immune cells and mediating inflammatory processes. It can influence the progression of inflammatory diseases and conditions in equine health. This page compiles peer-reviewed research studies and scholarly articles that investigate the expression, regulation, and implications of Tumor Necrosis Factor in equine physiology and pathology.
Siard-Altman MH, Harris PA, Moffett-Krotky AD, Ireland JL, Betancourt A, Barker VD, McMurry KE, Reedy SE, Adams AA.Similarly to aged humans, senior horses (≥20 years) exhibit chronic low-grade inflammation systemically, known as inflamm-aging. Inflamm-aging in the senior horse has been characterized by increased circulating inflammatory cytokines as well as increased inflammatory cytokine production by lymphocytes and monocytes in response to a mitogen. Little is currently known regarding underlying causes of inflamm-aging. However, senior horses are also known to present with muscle wasting and often the endocrinopathy pituitary pars intermedia dysfunction (PPID). Despite the concurrence of these phenom...
Brunner TJ, Lescun TB, Moore GE, Grady SE, Davern AJ, Taylor SD.The mechanism by which nonsteroidal anti-inflammatory drugs mitigate pain caused by a heart bar shoe (HBS) model of lameness is unknown. The purpose of this study was to determine if this HBS model of lameness induces inflammation in horses. Five healthy adult horses from a university teaching herd were enrolled. A custom HBS was applied to the left front foot of each horse, followed by induction of the American Association of Equine Practitioners Lameness Score of 4. Inflammatory markers including serum amyloid A (SAA) concentration, local venous tumor necrosis factor alpha and prostaglandin ...
Alicka M, Kornicka-Garbowska K, Kucharczyk K, Kępska M, Rӧcken M, Marycz K.Progressive loss of cell functionality caused by an age-related impairment in cell metabolism concerns not only mature specialized cells but also its progenitors, which significantly reduces their regenerative potential. Adipose-derived stem cells (ASCs) are most commonly used in veterinary medicine as an alternative treatment option in ligaments and cartilage injuries, especially in case of high-value sport horses. Therefore, the main aim of this study was to identify the molecular alternations in ASCs derived from three age-matched horse groups: young ( 15 years old). ASCs were isolated ...
Bauquier JR, Tennent-Brown BS, Tudor E, Bailey SR.Doramapimod (BIRB-796-BS), is an anti-inflammatory compound, acting through p38 MAPK inhibition, but its anti-inflammatory effects have not previously been studied in the horse. Whole blood aliquots from healthy horses diluted 1:1 with cell culture medium were incubated for 21 h with 1 μg/ml of lipopolysaccharide (LPS), lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of doramapimod (3 × 10 M to 10 M). Cell bioassays were used to measure TNF-α and IL-1β activity. Doramapimod significantly and potently inhibited TNF-α and IL-1β activity induced b...
Neuenschwander HM, Moreira JJ, Vendruscolo CP, Fülber J, Seidel SRT, Michelacci YM, Baccarin RYA.The intra-articular use of hyaluronic acid (HA) for the treatment of synovitis and osteoarthritis is still controversial. As a consequence, corticosteroids remain the most frequently employed therapeutic agents, despite their potential systemic and local deleterious effects. This study examined the anti-inflammatory, antioxidant, and chondroprotective activities of low and high molecular weight hyaluronic acid (LMW-HA and HMW-HA) on lipopolysaccharide (LPS)-induced synovitis in horses compared to triamcinolone acetonide (TA). LPS was injected in the metacarpophalangeal joints, which were treat...
Cvitas I, Galichet A, Ling SC, Müller EJ, Marti E.Thymic stromal lymphopoietin (TSLP) plays a key role in the development of allergic inflammation. Little is known about possible triggers of equine TSLP expression. Objective: To investigate TSLP expression in equine insect bite hypersensitivity (IBH) skin lesions. The capacity of TLR 1-8 ligands (L) and of atopic cytokine milieu as potential triggers of TSLP and of interleukin (IL)-6 as a downstream effector molecule of TLR signalling, were examined in primary equine keratinocyte cultures. Methods: Lesional skin from IBH-affected and healthy skin from control-horses (n = 9 each group) was s...
Shawaf T, El-Deeb WM, Elgioushy M.The aim of this study is to investigate the diagnostic efficiency of gastrin, pepsinogen, proinflammatory cytokines (TNF-α, IL-6), and oxidative stress biomarkers in horses with equine gastric ulcer syndrome (EGUS). Thirty horses diagnosed with gastroscopic EGUS and 15 clinically healthy horses were selected for this study. The serum levels of gastrin, pepsinogen showed nonsignificant changes in horses with EGUS when compared with healthy horses. The serum levels of TNF-α, IL-6 revealed a significant increase in horses with EGUS when compared with healthy ones. Oxidative stress is evident in...
Bond SL, Hundt J, Léguillette R.Mild equine asthma is a common inflammatory airway disease of the horse. The primary treatment of mild equine asthma is corticosteroids. The purpose of this study was to investigate the effects of injected dexamethasone on relative IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-17, IL-23, IFN-γ, Eotaxin-2 and TNF-α mRNA expression in bronchoalveolar lavage (BAL) fluid in healthy Thoroughbred horses (n = 6), and those with mild equine asthma (n = 7). Results: Horses with mild equine asthma had a significantly greater bronchoalveolar lavage mast cell percentage than healthy horses...
Chen JW, Stefanovski D, Haughan J, Jiang Z, Boston R, Soma LR, Robinson MA.Extracorporeal shockwave therapy (ESWT) can potentially mask painful injuries in equine athletes. Tests to detect whether a horse has received ESWT prior to competition are needed. Extracorporeal shockwave therapy is known to affect inflammatory mediators in other species, and if these mediators are altered in the horse, these could serve as biomarkers of ESWT. Objective: To test the hypothesis that a single application of ESWT will alter the circulating protein concentrations of 10 inflammatory mediators in horse plasma. Methods: Prospective repeated measures experimental study. Methods: Elev...
Samimi AS, Samimi K, Karimiafshar M, Tajik J.The objective of this study was to comparatively evaluate the anti-inflammatory effects of intravenous administration of insulin (in different doses) and flunixin on physiological variables, acute-phase responses, and cardiovascular biomarkers during inflammatory phase which was induced by Escherichia coli lipopolysaccharide (LPS) serotype O55:B5 in miniature donkeys. A total of twenty-four clinically healthy male adult miniature donkeys aged 5 ± 1 year and weighing 120 ± 10 kg were studied. The animals were assigned randomly to four experimental groups (three treatment and one positive co...
Cacciolatti C, Meyer-Ficca ML, Southwood LL, Meyer RG, Bertolotti L, Zarucco L.To evaluate effects of poly(ADP-ribose) polymerase-1 (PARP1) inhibitors on the production of tumor necrosis factor-α (TNF-α) by interferon-γ (IFN-γ)- and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) of horses as an in vitro model of inflammation in horses. Methods: 1,440 samples of PBMCs from 6 healthy research horses. Methods: From heparinized whole blood samples, PBMC cultures were obtained. An initial dose-response trial on 48 PBMC samples from 2 horses (24 samples each) was used to determine concentrations of IFN-γ and LPS for use as low- and high-lev...
Machado TSL, Massoco CO, Silva LCLC, Fülber J, Moreira JJ, Baccarin RYA.To compare effects of platelet-rich plasma (PRP), interleukin-1 receptor antagonist protein (IRAP), autologous processed plasma (APP), and sodium hyaluronate treatments on synovial fluid cells in vitro and on synovial fluid obtained from osteochondrotic joints of horses. Methods: Synovial fluid cells from 8 healthy equine tibiotarsal joints (in vitro experiment) and synovial fluid samples from 40 tibiotarsal joints of 25 horses with osteochondrosis dissecans (in vivo experiment). Methods: Effects of various treatments on concentrations of prostaglandin (PG) E2, interleukin (IL)-1β, tumor necr...
Hansen S, Otten ND, Fjeldborg J, Baptiste KE, Horohov DW.The objectives of this study were to evaluate the natural age-related variation and compare the level of pro-inflammatory cytokines in the peripheral blood and lower airways of horses. The mRNA expression of IL-1β, IL-6, IL-8 TNF-α TLR-4 in bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMC) were studied by quantitative real time polymerase chain reaction (PCR) and differential cell count cytology from 44 horses of different ages. A significant age-related increase was found for the mRNA expression of IL-6, IL-8, TLR-4 and TNF-α in stimulated BAL cells and for T...
Schedlbauer C, Blaue D, Gericke M, Blüher M, Starzonek J, Gittel C, Brehm W, Vervuert I.Non-alcoholic fatty liver disease is known as determining part of human obesity. The impact of body weight (BW) gain on liver metabolism has not been extensively investigated yet. Objective: To investigate hepatic alterations caused by increasing BW in ponies and horses. Methods: A total of 19 non-obese equines (10 Shetland ponies, geldings; nine Warmblood horses, geldings). Methods: Animals received 200% of their metabolizable maintenance energy requirements for 2 years. Serum alkaline phosphatase, glutamate dehydrogenase (GLDH), aspartate aminotransferase (AST), and gamma-glutamyl transferas...
Urayama S, Tanaka A, Kusano K, Sato H, Nagashima T, Fukuda I, Fujisawa C, Matsuda H.Nonsteroidal anti-inflammatory drugs such as flunixin meglumine have been used to treat signs of systemic inflammatory conditions, but it is also known to have the side effect to small intestine mucosa. It may be considered to be due to inhibition of both cyclooxygenase (COX)-1 and COX-2. On the other hand, meloxicam is widely used in equine clinical practice and an effective nonsteroidal anti-inflammatory drug with the preferential inhibitory effect on COX-2. However, it has not yet been evaluated in equine systemic inflammation. The aim of this study was to evaluate the effect of meloxicam a...
Rütten S, Schrödl W, Abraham G.Glucocorticoids are important drugs in the treatment of many inflammatory, autoimmune and allergic diseases in humans and animals. We investigated the effects of hydrocortisone and dexamethasone on TNF-α, IL-1Ra and INF-γ release in stimulated whole blood cell culture from healthy horses. Whole blood cell cultures proved to be useful for the characterization of the anti-inflammatory properties of new drugs. Diluted equine whole blood was exposed to lipopolysaccharide (LPS) and PCPwL (a cocktail consisting of phythemagglutinin E, concanavalin A, pokeweed mitogen and lipopolysaccharide) in the...
Broeckx SY, Pille F, Buntinx S, Van Brantegem L, Duchateau L, Oosterlinck M, Chiers K, Bertone AL, Spaas JH, Martens AM.OBJECTIVE To evaluate lameness and morphological changes associated with an osteochondral fragment-groove procedure as a means of experimental induction of metacarpophalangeal (MCP) joint osteoarthritis within an 11-week period in horses. ANIMALS 6 nonlame adult warmbloods. PROCEDURES The right MCP joint of each horse underwent an osteochondral fragment-groove procedure (day 0). After 1 week of stall rest (ie, starting day 7), each horse was trained daily on a treadmill. Weekly, horses underwent visual and inertial sensor-based assessments of lameness. Both MCP joints were assessed radiographi...
Ibrahim S, Szóstek-Mioduchowska A, Skarzynski D.Bacterial infections of the genital tract are the major cause of reproductive failure in the mares. MiRNAs are important regulators of gene expression, mostly through transcriptional and translational regression. We hypothesized that LPS induced aberrant expression of miRNAs and their targets, which are involved in regulation of uterine homeostasis. Three groups of primary endometrial epithelial and stromal cells, and endometrial tissue explants were cultured. The 1 group was kept as control, while the 2 and 3 groups were challenged with low (0.5 μg/mL) or high (3.0 μg/mL) doses of Lipop...
Jaworska J, Janowski T.Retained fetal membranes (RFM) is a prevalent postpartum disease in mares. During parturition, various proinflammatory cytokines are released in the placenta, which further facilitates uterine contractions, expulsion of the fetus and fetal membranes. We hypothesized that an altered inflammatory response in mares results in retained fetal membranes. Samples of the endometrium and the allantochorion were collected from 15 mares with RFM and from 29 control mares within 2 h of foal delivery. Next, the mRNA expression of IL-1β, IL-6 and TNFα proteins was analyzed by Real Time PCR and Western b...
Kornicka K, Śmieszek A, Węgrzyn AS, Röcken M, Marycz K.Endocrine disorders, including equine metabolic syndrome (EMS), are a serious issue in veterinary medicine and horse breeding. Furthermore, EMS was shown to affect the cytophysiological properties of adipose-derived stem cells, reducing their therapeutic potential. However, it was shown that those cells can be rejuvenated while using a combination of two chemicals: 5-azacytydine (AZA) and resveratrol (RES). In the present study, we decided to evaluate the immunomodulatory properties of AZA/RES-treated adipose-derived stem cells (ASC) isolated from EMS horses (ASC). Thus, we co-cultured ASC wit...
Martin EM, Schirmer JM, Jones SL, Davis JL.Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits anti-inflammatory effects in vivo in men and rodents, and inhibits TNFα production in equine leucocytes in vitro. Objective: Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFα production in an ex vivo inflammation model. Methods: Pharmacokinetic study, ex vivo experimental study. Methods: Six healthy adult horses ...
Bonilla-Gutiérrez AF, Castillo-Franz C, López C, Álvarez ME, Giraldo CE, Carmona JU.The aim of this study was to evaluate the release of pro- and anti-inflammatory as well as anabolic mediators stimulated by a leukocyte-reduced platelet-rich gel supernatant (Lr-PRGS) and a leukocyte-reduced plasma supernatant (Lr-PL) at two concentrations (25 and 50%) on normal equine suspensory ligament explants (SLEs) and tendon explants (TEs). SLEs and TEs from six horses were independently incubated for 48 h with Lr-PRGS and Lr-PL at concentrations of 25 and 50%, respectively. Samples were collected from the incubated tissues at 1 h and 48 h, which were employed for ELISA determinat...
Brandt L, Schubert S, Scheibe P, Brehm W, Franzen J, Gross C, Burk J.Transplantation of multipotent mesenchymal progenitor cells is a valuable option for treating tendon disease. Tenogenic differentiation leading to cell replacement and subsequent matrix modulation may contribute to the regenerative effects of these cells, but it is unclear whether this occurs in the inflammatory environment of acute tendon disease. Equine adipose-derived stromal cells (ASC) were cultured as monolayers or on decellularized tendon scaffolds in static or dynamic conditions, the latter represented by cyclic stretching. The impact of different inflammatory conditions, as represente...
Barrachina L, Remacha AR, Romero A, Vitoria A, Albareda J, Prades M, Roca M, Zaragoza P, Vázquez FJ, Rodellar C.This study aimed at assessing the effectiveness and safety of repeated administrations of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) primed with tumor necrosis factor (TNF)-α and interferon-γ in an equine model of chemically-induced osteoarthritis. Arthritis was induced in both radio-carpal (RC)-joints by amphotericin-B in 18 ponies, divided into three groups depending on the treatment injected: MSC-naïve (n = 7), MSC-primed (n = 7) and control (n = 4). The study consisted of two phases and used one RC-joint of each animal in each phase, with four months tim...
Montgomery JB, Husulak ML, Kosolofski H, Dos Santos S, Burgess H, Meachem MD.The objective of this study was to determine if TNF-α protein concentration differs in bronchoalveolar lavage fluid (BALF) obtained from healthy horses, horses with naturally occurring exacerbations of severe equine asthma and horses in remission from severe equine asthma. Tumor necrosis factor-alpha (TNF- α) protein concentrations were determined in BALF by commercial equine ELISA. Horses with naturally occurring exacerbation of severe equine asthma were found to have significantly lower BALF TNF-α protein concentrations than healthy horses (p = 0.0026). There was no significant differ...
Vendruscolo CDP, Moreira JJ, Seidel SRT, Fülber J, Neuenschwander HM, Bonagura G, Agreste FR, Baccarin RYA.The aim of this study was to verify whether transient inflammatory reactions induced by intra-articular medicinal ozone administration affect joint components, by in vivo evaluation of inflammatory (prostaglandin E2, Substance P, Interleukin-6, Interleukine-1, Tumor Necrosis Factor), anti-inflammatory (Interleukin-10) and oxidative (superoxide dismutase activity and oxidative burst) biomarkers and extracellular matrix degradation products (chondroitin sulphate and hyaluronic acid) in synovial fluid. The effects of medicinal ozone were analyzed at two ozone concentrations (groups A and B, 20 an...
Gabner S, Ertl R, Velde K, Renner M, Jenner F, Egerbacher M, Hlavaty J.A combination of tissue engineering methods employing mesenchymal stem cells (MSCs) together with gene transfer takes advantage of innovative strategies and highlights a new approach for targeting osteoarthritis (OA) and other cartilage defects. Furthermore, the development of systems allowing tunable transgene expression as regulated by natural disease-induced substances is highly desirable. Bone marrow-derived equine MSCs were transduced with a lentiviral vector expressing interleukin-1 receptor antagonist (IL-1Ra) gene under the control of an inducible nuclear factor-kappa B-responsive prom...
Vanderstock JM, Lecours MP, Lavoie-Lamoureux A, Gottschalk M, Segura M, Lavoie JP, Jean D.OBJECTIVE To evaluate in vitro phagocytosis and bactericidal activity of circulating blood neutrophils in horses with severe equine asthma and control horses and to determine whether circulating blood neutrophils in horses with severe equine asthma have an increase in expression of the proinflammatory cytokine tumor necrosis factor (TNF)-α and the chemokine interleukin (IL)-8 and a decrease in expression of the anti-inflammatory cytokine IL-10 in response to bacteria. ANIMALS 6 horses with severe equine asthma and 6 control horses. PROCEDURES Circulating blood neutrophils were isolated from h...
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...
Naskou MC, Sumner SM, Chocallo A, Kemelmakher H, Thoresen M, Copland I, Galipeau J, Peroni JF.Mesenchymal stem cells (MSCs) produced for clinical purposes rely on culture media containing fetal bovine serum (FBS) which is xenogeneic and has the potential to significantly alter the MSC phenotype, rendering these cells immunogenic. As a result of bovine-derived exogenous proteins expressed on the cell surface, MSCs may be recognized by the host immune system as non-self and be rejected. Platelet lysate (PL) may obviate some of these concerns and shows promising results in human medicine as a possible alternative to FBS. Our goal was to evaluate the use of equine platelet lysate (ePL) poo...
Gabner S, Ertl R, Velde K, Renner M, Jenner F, Egerbacher M, Hlavaty J.A combination of tissue engineering methods employing mesenchymal stem cells (MSCs) together with gene transfer takes advantage of innovative strategies and highlights a new approach for targeting osteoarthritis (OA) and other cartilage defects. Furthermore, the development of systems allowing tunable transgene expression as regulated by natural disease-induced substances is highly desirable. Bone marrow-derived equine MSCs were transduced with a lentiviral vector expressing interleukin-1 receptor antagonist (IL-1Ra) gene under the control of an inducible nuclear factor-kappa B-responsive prom...
Naskou MC, Norton NA, Copland IB, Galipeau J, Peroni JF.Platelet lysate (PL) has been extensively used for the laboratory expansion of human mesenchymal stem cells (MSC) in order to avoid fetal bovine serum (FBS) which has been associated with immune-mediated host reactions and transmission of bovine-origin microbial contaminants. Before suggesting the routine use of PL for MSC culture, we wanted to further investigate whether PL alone might trigger inflammatory responses when exposed to reactive white blood cells such as monocytes. Our objectives were to evaluate the inflammatory profile of equine monocytes cultured with equine PL (ePL) and to det...
Morris DD, Crowe N, Moore JN.Serum tumor necrosis factor (TNF) activity was quantitated in 8 horses given an IV infusion of endotoxin (0.03 micrograms of lipopolysaccharide/kg of body weight, from Escherichia coli 055:B5) in 0.9% NaCl solution over 1 hour. Serum TNF activity was likewise measured in 6 horses given only 0.9% sterile NaCl solution at the same rate. The duration of serum TNF activity was determined, and serum TNF activity was correlated with clinical and laboratory changes during the induced endotoxemia. Horses had no serum TNF activity prior to endotoxin administration, but geometric mean serum TNF activity...
Marchetti B, Gault EA, Cortese MS, Yuan Z, Ellis SA, Nasir L, Campo MS.Bovine papillomavirus type 1 is one of the aetiological agents of equine sarcoids. The viral major oncoprotein E5 is expressed in virtually all sarcoids, sarcoid cell lines and in vitro-transformed equine fibroblasts. To ascertain whether E5 behaves in equine cells as it does in bovine cells, we introduced the E5 open reading frame into fetal equine fibroblasts (EqPalF). As observed in primary bovine fibroblasts (BoPalF), E5 by itself could not immortalize EqPalF and an immortalizing gene, such as human telomerase (hTERT/hT), was required for the cells to survive selection. The EqPalF-hT-1E5 c...
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...
Moore BD, Balasuriya UB, Watson JL, Bosio CM, MacKay RJ, MacLachlan NJ.Equine arteritis virus (EAV) infects endothelial cells (ECs) and macrophages in horses, and many of the clinical manifestations of equine viral arteritis (EVA) reflect vascular injury. To further evaluate the potential role of EAV-induced, macrophage-derived cytokines in the pathogenesis of EVA, we infected cultured equine alveolar macrophages (AMphi), blood monocyte-derived macrophages (BMphi), and pulmonary artery ECs with either a virulent (KY84) or an avirulent (CA95) strain of EAV. EAV infection of equine AMphi, BMphi, and ECs resulted in their activation with increased transcription of g...
Olave CJ, Ivester KM, Couetil LL, Kritchevsky JE, Tinkler SH, Mukhopadhyay A.Respirable dust exposure is linked to airway inflammation in racehorses. Feeding haylage may reduce dust exposure by 60-70%. The objective of this study was to compare dust exposure, airway cytology, and inflammatory cytokine concentrations between horses fed haylage or hay over 6 weeks while in training. Seven healthy Standardbred horses were randomly assigned to be fed alfalfa hay (n = 3) or grass-alfalfa mix haylage (n = 4) for six weeks while training on a treadmill. Dust exposure was measured gravimetrically at the breathing zone. Endotoxin and β-glucan concentrations in respirable dust ...
Kim HY, Mott J, Zhi N, Tajima T, Rikihisa Y.Human granulocytic ehrlichiosis (HGE), a tick-borne zoonosis, is caused by an obligatory intragranulocytic bacterium, the HGE agent, a strain of Anaplasma phagocytophila. The equine model of HGE is considered valuable in understanding pathogenic and immune mechanisms of HGE. In the present study, cytokine mRNA expression by peripheral blood leukocytes (PBLs) in horses was examined during the course of infection by intravenous inoculation of A. phagocytophila or by allowing feeding by infected ticks. The p44 genes encoding the major outer membrane protein P44s of A. phagocytophila were detected...
Hosaka Y, Kirisawa R, Ueda H, Yamaguchi M, Takehana K.Tumor necrosis factor (TNF) receptors (TNF-R)-mediated cell survival or apoptosis has been demonstrated in many cells, but little is known about survival or apoptotic signals via TNF-R1 in tendinocytes. In this study, we focused on four signaling factors, TNFalpha, TNF-R1, TNFR-associated factor2 (TRAF2) and caspase-3, in order to elucidate the signaling events in tendinocytes. Samples were obtained from normal, inflamed and scar-formed equine superficial digital flexor tendons. To detect these signaling factors, samples were subjected to immunohistochemistry and Western blot analysis, and som...
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...
Siard MH, McMurry KE, Adams AA.Senior horses (aged ≥ 20 years) exhibit increased chronic, low-grade inflammation systemically, termed inflamm-aging. Inflammation is associated with many afflictions common to the horse, including laminitis and osteoarthritis, which are commonly treated with the non-steroidal anti-inflammatory drugs (NSAIDs) flunixin meglumine and phenylbutazone. Although these NSAIDs are effective in treating acute inflammatory problems, long-term treatment with NSAIDs can result in negative side effects. Thus, bioactive polyphenols including curcuminoids, resveratrol, quercetin, pterostilbene, and hydroxy...
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, ...
Ríos DL, López C, Álvarez ME, Samudio IJ, Carmona JU.Platelet-rich plasma (PRP) preparations are a common treatment in osteoarthritis (OA) and inflammatory synovitis. However, there is ambiguity regarding the ideal concentration of leukocytes and platelets in these preparations necessary to induce an adequate anti-inflammatory and anabolic response in joint tissues, such as the synovial membrane. This research aimed to study, in normal synovial membrane explants (SME) challenged with lipopolysaccharide (LPS), the temporal effects (at 48 and 96h) of leukocyte- and platelet-rich gel (L-PRG) and pure platelet-rich gel (P-PRG) supernatants on the pr...
Hawkins DL, MacKay RJ, Gum GG, Colahan PT, Meyer JC.In each of 4 horses, sterile synovitis was induced by intra-articular injection of 3 micrograms of Escherichia coli endotoxin (lipopolysaccharide, LPS) into one antebrachiocarpal joint; an equal volume (2 ml) of phosphate-buffered saline solution (PBSS) was injected into the opposite, control carpus. Blood and 1.5 ml of synovial fluid were obtained at postinjection hours (PIH) 0, 2, 4, 8, 12, 18, 42, 66, and 144. Synovial fluid sample collection was accomplished by use of an indwelling, intra-articular catheter through PIH 12, and by arthrocentesis subsequently. Joint fluid samples were analyz...
Morris DD, Moore JN, Crowe N.Over a 24-month period, serum tumor necrosis factor (TNF) activity was determined in 289 horses with colic attributable to gastrointestinal tract disease. Serum TNF activity was quantitated by use of a modified in vitro cytotoxicity bioassay, using WEHI 164 clone-13 murine fibrosarcoma cells. Causes for colic, determined by clinical and laboratory evaluation, exploratory celiotomy, or necropsy included: gastrointestinal tract rupture (GTR); ileal impaction; small intestinal strangulating obstruction (SIO); proximal enteritis (PE); transient small intestinal distention; large-colon displacement...
Peiró JR, Barnabé PA, Cadioli FA, Cunha FQ, Lima VM, Mendonça VH, Santana AE, Malheiros EB, Perri SH, Valadão CA.The clinical efficacy of IV infusion of lidocaine for treatment of equine endotoxemia has not been studied. Objective: Lidocaine infusion after exposure to lipopolysaccharide (LPS) will inhibit the inflammatory response and have inhibitory effects on the hemodynamic and cytokine responses to endotoxemia. Methods: Twelve horses. Methods: Two equal groups (n=6): saline (GI) and lidocaine (GII). In all animals, endotoxin (500 ng/kg body weight [BW]) was injected intraperitoneally over 5 minutes. Twenty minutes later, animals received a bolus of GI or GII (1.3 mg/kg BW) over 5 minutes, followed by...
Miller AB, Harris PA, Barker VD, Adams AA.Long-distance transport is associated with stress-related changes in equine immune function, and shipping-associated illnesses are often reported. Horses are frequently transported short distances, yet the effects of short-term transport on immune function remain largely unknown. Twelve horses, aged 15-30 yr, were assigned to either the control (n = 6) or treatment (n = 6) groups; treatment horses received a daily antioxidant supplement 3 weeks before and after transport. All horses were transported for approximately 1.5-2 hr on Day 0. Blood was collected via jugular venipuncture at 15-min pre...
Loftus JP, Black SJ, Pettigrew A, Abrahamsen EJ, Belknap JK.To determine proinflammatory gene expression, endothelial adhesion molecule gene expression, and matrix metalloproteinase (MMP) concentrations in laminar specimens at 1.5 hours after administration of black walnut extract (BWE) and to compare these values with later time points. Methods: 25 horses. Methods: After nasogastric administration of BWE, anesthesia was induced at 1.5 hours in early time point (ETP) horses (n = 5), between 3 and 4 hours in developmental time point horses (5), and between 9 and 10 hours in acute onset of lameness time point horses (5). Anesthesia was induced at 3 and 1...
Menzies-Gow NJ, Wray H, Bailey SR, Harris PA, Elliott J.The mechanisms underlying predisposition to pasture-associated laminitis remain unclear; chronic inflammation is implicated, and this may be exacerbated by physical inactivity. Objective: To determine whether exercise affects the inflammatory profile of normal and previously laminitic ponies. Methods: Prospective case-control study. Methods: The short (1 day) and longer term (14 days) effects of low intensity (10 min walking and 5 min trotting) exercise on plasma inflammatory marker concentrations in normal (NL) and previously laminitic (PL) nonobese ponies (n = 6/group) was determined. Plasma...
Palm F, Walter I, Budik S, Kolodziejek J, Nowotny N, Aurich C.After artificial insemination or mating an inflammatory response is induced by spermatozoa and components of the inseminate or ejaculate. In order to investigate the inflammatory reaction of the endometrium to different semen extenders, phosphate buffered saline (PBS), seminal plasma (SP), skim milk-based extender (SM) or egg yolk semen extender (EY) was inoculated into the uterus of oestrous mares (n=8) during four consecutive cycles in alternating order. Twelve hours after treatment, a uterine lavage was performed and an endometrial biopsy was taken. An additional biopsy was taken in the oes...
Lohmann KL, Vandenplas M, Barton MH, Moore JN.Endotoxemia is associated with the principal causes of death in adult horses and equine neonates and, therefore, veterinary researchers are expending efforts to identify new therapeutic interventions that might be beneficial in these animals. Endotoxin antagonists inhibit interaction of endotoxin with cellular receptors and may be beneficial in the treatment of endotoxemia and sepsis. Diphosphoryl lipid A from Rhodobacter sphaeroides (RsDPLA) is a potent antagonist of enteric LPS in human cells, but is an agonist in hamster cells. In this study, the effect of lipopolysaccharide from R. sphaero...
Wray H, Elliott J, Bailey SR, Harris PA, Menzies-Gow NJ.The mechanisms underlying individual animal predisposition to pasture-associated laminitis remain unclear; however, chronic inflammation is implicated. Objective: To identify differences in the inflammatory profile of a group of previously laminitic ponies compared with control animals at pasture in late spring and winter. Methods: Previously laminitic (PL; n = 38 and 42) and nonlaminitic control ponies (NL; n = 41 and 39) were sampled in late spring and winter. Body condition score, height, weight and crest height and thickness were measured. Plasma concentrations of tumour necrosis factor-α...
Tadros EM, Frank N, Donnell RL.To test the hypothesis that inflammatory responses to endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). Animals-6 healthy horses and 6 horses with EMS. Methods: Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline data were obtained 30 minutes before each infusion. After infusion, a physical examination was performed hourly for 9 hours and at 15 and 21 hours; a whole blood sample was collect...
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...
Berghaus LJ, Giguère S, Bordin AI, Cohen ND.Rhodococcus equi is a common cause of pneumonia in foals and an opportunistic pathogen in immunosuppressed people. The ability of R. equi to survive and replicate in macrophages is the basis of its pathogenicity. Limited knowledge about the role of cytokines in host defense against R. equi comes from studies in mice and the role of cytokines in intracellular survival of R. equi in equine macrophages is unknown. The objectives of this study were to determine the effect of priming with interferon (IFN)-γ, interleukin (IL)-1β, IL-4, IL-6, IL-10, or tumor necrosis factor (TNF)-α at various conc...
Kearney CM, Khatab S, van Buul GM, Plomp SGM, Korthagen NM, Labberté MC, Goodrich LR, Kisiday JD, Van Weeren PR, van Osch GJVM, Brama PAJ.Allogenic mesenchymal stem cell (MSC) secretome is a novel intra-articular therapeutic that has shown promise in and small animal models and warrants further investigation. Unassigned: To investigate if intra-articular allogenic MSC-secretome has anti-inflammatory effects using an equine model of joint inflammation. Unassigned: Randomized positively and negatively controlled experimental study. Unassigned: In phase 1, joint inflammation was induced bilaterally in radiocarpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After 2 h, the secretome of INFy and TNFα stimul...
Zhang B, Sun C, Jin S, Cascio M, Montelaro RC.The equine lentivirus receptor 1 (ELR1), a member of the tumor necrosis factor receptor (TNFR) protein family, has been identified as a functional receptor for equine infectious anemia virus (EIAV). Toward defining the functional interactions between the EIAV SU protein (gp90) and its ELR1 receptor, we mapped the gp90 binding domain of ELR1 by a combination of binding and functional assays using the EIAV SU gp90 protein and various chimeric receptor proteins derived from exchanges between the functional ELR1 and the nonbinding homolog, mouse herpesvirus entry mediator (murine HveA). Complement...
Ley C, Ekman S, Elmén A, Nilsson G, Eloranta ML.The carpal joints are common sites of traumatic arthritis and osteoarthritis (OA) in athletic horses. The pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF) may be of great importance in the development of intra-articular lesions. The aim of the present study was to investigate possible associations between synovial fluid levels of bioactive IL-6 and TNF and different types of joint lesions seen in traumatic arthritis and OA. Synovial fluid was collected from horses with carpal lameness immediately before arthroscopic surgery. Articular cartilage, synovial membranes...
Valigura HC, Leatherwood JL, Martinez RE, Norton SA, White-Springer SH.Mitigation of exercise-induced stress is of key interest in determining ways to optimize performance horse health. To test the hypothesis that dietary supplementation of a Saccharomyces cerevisiae fermentation product would decrease markers of exercise-induced stress and inflammation in young horses, Quarter Horse yearlings (mean ± SD; 9 ± 1 mo) were randomly assigned to receive either no supplementation (CON; n = 8) or 21 g/d S. cerevisiae fermentation product (10.5 g/feeding twice daily; SCFP; n = 10) top-dressed on a basal diet of custom-formulated grain as well as ad libitum Coastal berm...
MacKay RJ, Merritt AM, Zertuche JM, Whittington M, Skelley LA.Serum and plasma from horses injected with endotoxin was examined for cytotoxic activity. Each of the cell lines, L929 and WEHI 164 clone 13, was sensitive to the cytotoxic effects of equine serum; however, a precipitation artifact caused by the use of isopropanol in the WEHI assay limited the use of this assay to samples containing less than 2 mg of protein/ml. In foals treated with a sublethal IV bolus of 5 micrograms of lipopolysaccharide (LPS)/kg and in adult horses given a low-dose continuous infusion of LPS (30 ng/kg/h for 4 hours), cytotoxic activity was detected in all serum or plasma ...
