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.
Barton AK, Richter IG, Ahrens T, Merle R, Alalwani A, Lilge S, Purschke K, Barnewitz D, Gehlen H.The purpose of the study was to compare the results of sepsis scoring (clinical examination and clinical pathology) to the concentrations of matrix-metalloproteinases (MMPs) -2, -8, and -9; tissue-inhibitor of metalloproteinases (TIMPs) -1 and -2; and inflammatory chemokines interleukin (IL) 1β and tumor-necrosis-factor-alpha (TNF-α) in plasma and peritoneal fluid of equine colic patients. A modified sepsis scoring including general condition, heart and respiratory rate, rectal temperature, mucous membranes, white blood cell count (WBC), and ionized calcium was applied in 47 horses presented...
Anderson SL, Duke-Novakovski T, Robinson AR, Townsend HGG, Singh B.The objective of this study was to determine the effect of pulmonary intravascular macrophage depletion on systemic inflammation and ex vivo neutrophil apoptosis using an experimental model of intestinal ischemia and reperfusion injury in horses. Neutrophils were isolated before and after surgery from horses that were randomized to three treatment groups, namely, sham celiotomy (CEL, = 4), intestinal ischemia and reperfusion (IR, = 6), and intestinal ischemia and reperfusion with gadolinium chloride treatment to deplete pulmonary intravascular macrophages (PIMs, IRGC, = 6). Neutrophil apopt...
Gugliandolo E, Crupi R, Biondi V, Licata P, Cuzzocrea S, Passantino A.Although inflammation is an important physiological response, it plays a prominent role in several diseases across the mammalian species. In horses, in particular, inflammation secondary to bacterial infection or translocation is one of the most frequent causes of morbidity and mortality. Research in new molecules with anti-inflammatory and immunomodulatory proprieties and safe use profile is constantly an active field; natural compounds are an important source of molecules with peculiar properties such as antioxidants, anti-inflammatory and immune modulating. Silibinin, a natural polyphenolic...
Kim KH, Park TS, Cho BW, Kim TM.Recent studies have shown that mesenchymal stem cells (MSCs) can play a restorative role against degenerative joint diseases in horses. The purpose of this study was to investigate whether fetal bone marrow-derived cells (BMC)-derived nanoparticles (BMC-NPs) can stimulate the survival of equine chondrocytes. Equine fetal BMCs were isolated and characterized, and the role of BMC-NPs s in equine chondrocytes undergoing inflammatory cell death was examined. BMCs have several characteristics, such as the potential to differentiate into chondrocytes and osteocytes. Additionally, BMCs expressed immu...
Anderson JR, Phelan MM, Foddy L, Clegg PD, Peffers MJ.Osteoarthritis is an age-related degenerative musculoskeletal disease characterized by loss of articular cartilage, synovitis, and subchondral bone sclerosis. Osteoarthritis pathogenesis is yet to be fully elucidated with no osteoarthritis-specific biomarkers in clinical use. equine cartilage explants ( = 5) were incubated in tumor necrosis factor-α (TNF-α)/interleukin-1β (IL-1β)-supplemented culture media for 8 days, with the media removed and replaced at 2, 5, and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent one-d...
Bauquier J, Tudor E, Bailey S.Doramapimod, a p38 MAPK inhibitor, is a potent anti-inflammatory drug that decreases inflammatory cytokine production in equine whole blood in vitro. It may have benefits for treating systemic inflammation in horses. Objective: To determine whether doramapimod is well tolerated when administered IV to horses, and whether it has anti-inflammatory effects in horses in a low-dose endotoxemia model. Methods: Six Standardbred horses. Methods: Tolerability study, followed by a blinded, randomized, placebo-controlled cross-over study. Horses were given doramapimod, and clinical and clinicopathologica...
Jeremiasse B, Matta C, Fellows CR, Boocock DJ, Smith JR, Liddell S, Lafeber F, van Spil WE, Mobasheri A.Chondrocytes are exposed to an inflammatory micro-environment in the extracellular matrix (ECM) of articular cartilage in joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). In OA, degenerative changes and low-grade inflammation within the joint transform the behaviour and metabolism of chondrocytes, disturb the balance between ECM synthesis and degradation, and alter the osmolality and ionic composition of the micro-environment. We hypothesize that chondrocytes adjust their physiology to the inflammatory microenvironment by modulating the expression of cell surface prote...
Stokes SM, Burns TA, Watts MR, Bertin FR, Stefanovski D, Medina-Torres CE, Belknap JK, van Eps AW.Continuous digital hypothermia (CDH) prevents lamellar failure in the euglycemic hyperinsulinemic clamp (EHC) model of laminitis, but the protective mechanisms are unclear. Objective: To determine if CDH inhibits lamellar inflammatory signaling in the EHC model of laminitis. Methods: Eight Standardbred horses. Methods: Prospective experimental study. Horses underwent an EHC, with 1 forelimb treated with CDH and the other kept at ambient temperature (AMB). Horses were euthanized 48 hours after initiation of the EHC and lamellar tissue was analyzed via polymerase chain reaction (pro-inflammato...
Caffi V, Espinosa G, Gajardo G, Morales N, Durán MC, Uberti B, Morán G, Plaza A, HenrÃquez C.Mesenchymal stem/stromal cells (MSCs) are increasingly explored for the treatment of degenerative and inflammatory diseases in human and veterinary medicine. One of the key characteristics of MSCs is that they modulate inflammation mainly through the secretion of soluble mediators. However, despite widespread clinical use, knowledge regarding the effector mechanisms of equine MSCs, and consequently their effectiveness in the treatment of diseases, is still unknown. The objectives of this study were to determine the mechanisms underlying inhibition of lymphocyte proliferation by equine bone mar...
Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A.Little information is available about endotoxemia in donkeys. Characterizing the systemic inflammatory response (SIRS) to lipopolysaccharide (LPS) in donkeys would provide valuable clinical and therapeutic information. The effects of meloxicam on endotoxemia have not been studied in this species. Objective: To study the pathophysiology and gene expression associated with experimentally induced endotoxemia, and evaluate the effects of meloxicam on experimentally induced endotoxemia in donkeys and in equine monocyte cultures. Methods: Six healthy adult female donkeys. Methods: Endotoxemia was in...
Connelly C, Norton NA, Hurley DJ, Hart KA, Meichner K, Gogal RM.Peripheral blood is commonly sampled to assess the health status of human and veterinary patients. Venous blood collection is a minimally invasive procedure, and in the horse, the common collection site is the jugular vein. Post blood collection, sample processing for leukocyte enrichment can vary by research laboratory with the potential to yield different effects on the enriched cells and their function. The focus of the present study was to compare a common blood dilution-leukocyte enrichment technique using a Histopaque gradient medium (His) to a modified leukocyte buffy coat syringe-lymph...
Page AE, Adam E, Stewart JC, Gonzales C, Barker V, Horohov DW.While the use of lipopolysaccharide (LPS) to induce inflammation has been well described in the horse, the object of this study was to evaluate the effect of repeated intra-articular LPS injections and determine whether this method may be of use to assess changes in gene expression related to inflammation. Six mixed breed horses were utilized for this study, with three horses aged 10-17 years (older group) and three horses aged 3 years (younger group). One milliliter of phosphate-buffered saline containing 3 μg of LPS from Escherichia coli O111:B4 was aseptically injected into either the radi...
Sotelo EDP, Vendruscolo CP, Fülber J, Seidel SRT, Jaramillo FM, Agreste FR, Silva LCLCD, Baccarin RYA.Several studies in human and equine medicine have produced controversial results regarding the role of dimethylsulfoxide (DMSO) as a therapeutic agent. This study aimed to evaluate the effect of joint lavage with different DMSO concentrations on biomarkers of synovial fluid inflammation and cartilage degradation in joints with lipopolysaccharide (LPS)-induced synovitis. Twenty-six tibiotarsal joints of 13 horses were randomly distributed into four groups (lactated Ringer's solution; 5% DMSO in lactated Ringer's; 10% DMSO in lactated Ringer's; and sham). All animals were evaluated for the prese...
Fagan MM, Harris P, Adams A, Pazdro R, Krotky A, Call J, Duberstein KJ.Vitamin E is an essential antioxidant that may benefit athletes by reducing oxidative stress and influencing cytokine expression. Supplements can be derived from natural or manufactured synthetic sources. This study aimed to determine (1) if supplemental vitamin E is beneficial to exercising horses and (2) if there is a benefit of natural versus synthetic vitamin E. After 2 weeks on the control diet (vitamin E-deficient grain and hay), 18 horses were divided into three groups and fed the control diet plus (1) 1000 IU/d synthetic α-tocopherol (SYN-L), (2) 4000 IU/d synthetic α-tocopherol (SYN...
Steuer AE, Stewart JC, Barker VD, Adams AA, Nielsen MK.The role of the immune response to cyathostomin infections in horses remains unknown. Intestinal goblet cell hyperplasia has previously been noted as a component in cyathostomin infection; however, the function is unclear. The goal of this study was to evaluate the local and systemic gene expression to cyathostomin infections following larvicidal treatment and explore their relation to goblet cells. Thirty-six ponies with naturally acquired cyathostomin infections were randomly allocated into three groups: fenbendazole-treated (10Â mg/kg PO 5Â days), moxidectin-treated (0.4Â mg/kg PO once) and...
Lange-Consiglio A, Romele P, Magatti M, Silini A, Idda A, Martino NA, Cremonesi F, Parolini O.Equine amniotic mesenchymal stromal cells (AMSCs) and their conditioned medium (CM) were evaluated for their ability to inhibit in vitro proliferation of peripheral blood mononuclear cells (PBMCs) with and without priming. Additionally, AMSC immunogenicity was assessed by expression of MHCI and MHCII and their ability to counteract the in vitro inflammatory process. Horse PBMC proliferation was induced with phytohemagglutinin. AMSC priming was performed with 10 ng/ml of TNF-α, 100 ng/ml of IFN-γ, and a combination of 5 ng/ml of TNF-α and 50 ng/ml of IFN-γ. The CM generated from naÃ...
Bruschetta G, D'Ascola A, Medica P, Ferlazzo AM.Serotonin (5-hydroxytryptamine [5-HT]) may induce metabolic effects in different cell types, including leukocytes. In horses, 5-HT is involved in physiological and behavioral functions. Physical exercise is known to increase the amounts of 5-HT both in brain and periphery, but so far, the signal mechanism in response to exercise is not known. The aim of the study was to investigate the effect of a racehorse intensive training session on plasma 5-HT levels, serotonin transporter (SERT), 5HT, 5-HT, 5-HT, 5-HT receptor, interleukin-1 beta, and tumor necrosis factor-alpha expression in horse perip...
J Rgensen E, Hjerpe FB, Hougen HP, Bjarnsholt T, Berg LC, Jacobsen S.To evaluate histologic changes and gene expression patterns in body and limb wounds in horses in response to bacterial inoculation. Methods: Wound biopsy specimens from 6 horses collected on days 7, 14, 21, and 27 after excisional wounds (20 wounds/horse) were created over the metacarpal and metatarsal region and lateral thoracic region (body) and then inoculated or not inoculated on day 4 with Staphylococcus aureus and Pseudomonas aeruginosa. Methods: Specimens were histologically scored for the amount of inflammation, edema, angiogenesis, fibrosis organization, and epithelialization. Quantit...
Mostafavi E, Esmaeilnejad B, Meysam Abtahi Foroushani S.This study was undertaken to assess the effects of T. equi infection on serum concentrations of some important cytokines including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-1 beta (IL-1β), IL-1α, IL-4, IL-6, IL-8, IL-10, IL-12α, IL-12β, IL-18, as well as total, protein and lipid binding sialic acids (TSA, PBSA and LBSA). Furthermore, any probable relation among the parasitemia, cytokines and sialic acids (SAs) were calculated using Pearson correlation and simple linear regression. Almost 300 draft horses (Kurdish-breed) with age of 3-4 years old from north-...
Martin LM, Johnson PJ, Amorim JR, DeClue AE.Resveratrol, a phytophenol, is a commonly used equine nutraceutical supplement touted to exert anti-inflammatory effects. The effect of orally administered resveratrol on tumor necrosis factor (TNF), interleukin-1β (IL-1β), leukocyte phagocytic activity or oxidative burst function have not been reported in horses. The objective of this study was to determine the effects of a commercially available, orally administered resveratrol product on innate immune functions in healthy adult horses. Whole blood was collected from 12 horses prior to and following 3 weeks of treatment with either the man...
Delco ML, Goodale M, Talts JF, Pownder SL, Koff MF, Miller AD, Nixon B, Bonassar LJ, Lundgren-Åkerlund E, Fortier LA.Early intervention with mesenchymal stem cells (MSCs) after articular trauma has the potential to limit progression of focal lesions and prevent ongoing cartilage degeneration by modulating the joint environment and/or contributing to repair. Integrin α10β1 is the main collagen type II binding receptor on chondrocytes, and MSCs that are selected for high expression of the α10 subunit have improved chondrogenic potential. The ability of α10β1-selected (integrin α10high) MSCs to protect cartilage after injury has not been investigated. To investigate integrin α10high MSCs to prevent postt...
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...
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...
Vick MM, Murphy BA, Sessions DR, Reedy SE, Kennedy EL, Horohov DW, Cook RF, Fitzgerald BP.To determine whether an inflammatory challenge induces insulin resistance in horses and examine possible contributions of adipose tissue to inflammatory cytokine production. Methods: 15 adult mares. Methods: Lipopolysaccharide (0.045 mug/kg, IV) or saline solution was administered, and insulin sensitivity was determined by means of the hyperinsulinemic, euglycemic clamp procedure or an adipose tissue biopsy was performed. Adipose tissue samples were collected, and mature adipocytes were obtained. Mature adipocytes were stimulated with lipopolysaccharide or dedifferentiated into preadipocytes a...
Jacobs CC, Holcombe SJ, Cook VL, Gandy JC, Hauptman JG, Sordillo LM.Endotoxaemia contributes to morbidity and mortality in horses with colic due to inflammatory cascade activation. Effective therapeutic interventions are limited for these horses. Ethyl pyruvate (EP), an anti-inflammatory agent that alters the expression of proinflammatory cytokines, improved survival and organ function in sepsis and gastrointestinal injury in rodents and swine. Therapeutic efficacy of EP is unknown in endotoxaemic horses. Objective: Determine the effects of EP on signs of endotoxaemia and expression of proinflammatory cytokines following administration of lipopolysaccharide (L...
Belknap JK, Giguère S, Pettigrew A, Cochran AM, Van Eps AW, Pollitt CC.Recent research has indicated that inflammation plays a role in the early stages of laminitis and that, similar to organ failure in human sepsis, early inflammatory mechanisms may lead to downstream events resulting in lamellar failure. Characterisation of the type of immune response (i.e. innate vs. adaptive) is essential in order to develop therapeutic strategies to counteract these deleterious events. Objective: To quantitate gene expression of pro-inflammatory cytokines known to be important in the innate and adaptive immune response during the early stages of laminitis, using both the bla...
Parbhakar OP, Duke T, Townsend HG, Singh B.Horses are unique in their extreme sensitivity to endotoxin-induced cardio-pulmonary shock and mortality. The mechanisms behind increased sensitivity of the horse to endotoxin remain unknown. Pulmonary intravascular macrophages (PIMs) are pro-inflammatory cells occurring in horses. Because the functions of equine PIMs in endotoxemia remain unknown, we studied the role played by equine PIMs in endotoxin-induced pulmonary pathophysiology. We achieved this by using a recently developed protocol to deplete PIMs in order to compare lipopolysaccharide (LPS)-induced pulmonary responses in horses with...
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...
Barton MH, Parviainen A, Norton N.A safe, affordable and effective treatment for endotoxaemia in horses is needed in order to reduce the incidence of this potentially fatal condition. Objective: To evaluate the effect of polymyxin B (PMB) on signs of experimentally-induced endotoxaemia. Objective: PMB ameliorates the adverse effects of endotoxaemia without causing nephrotoxicity. Methods: Four groups of 6 healthy mature horses each received 20 ng endotoxin/kg bwt i.v. over 30 mins. Additionally, each group received one of the following i.v.; 5000 u PMB/kg bwt 30 mins before endotoxin infusion; 5000 u PMB/kg bwt 30 mins after e...
Tanabe S, Suzuki T, Wasano Y, Nakajima F, Kawasaki H, Tsuda T, Nagamine N, Tsurumachi T, Sugaya K, Akita H, Takagi M, Takagi K, Inoue Y, Asai Y....We previously isolated the commensal bacteria lactobacilli and bifidobacteria from the Thoroughbred intestine and prepared the horse probiotics LacFi(TM), consisting of Lactobacillus ruminis KK14, L. equi KK 15, L. reuteri KK18, L. johnsonii KK21, and Bifidobacterium boum HU. Here, we found that the five LacFi(TM) constituent strains remarkably suppressed pro-inflammatory interleukin-17 production in mouse splenocytes stimulated with interleukin-6 and transforming growth factor-β. The protective effects of the probiotic on impaired intestinal barrier function were evaluated in Caco-2 cells tr...
Fasanello DC, Su J, Deng S, Yin R, Colville MJ, Berenson JM, Kelly CM, Freer H, Rollins A, Wagner B, Rivas F, Hall AR, Rahbar E, DeAngelis PL....TNF-α-stimulated gene 6 (TSG-6) protein, a TNF-α-responsive hyaladherin, possesses enzymatic activity that can catalyze covalent crosslinks of the polysaccharide hyaluronic acid (HA) to another protein to form heavy chain-hyaluronic acid (HC-HA) complexes in pathological conditions such as osteoarthritis (OA). Here, we examined HA synthase and inflammatory gene expression; synovial fluid HA, TNF-α, and viscosity; and TSG-6-mediated HC-HA complex formation in an equine OA model. The objectives of this study were to (1) evaluate the TNF-α-TSG-6-HC-HA signaling pathway across multiple joint t...
Fjordbakk CT, Johansen GM, Løvås AC, Oppegård KL, Storset AK.No recommendations have been made regarding the relative timing of blood collection for autologous conditioned serum (ACS) preparation and surgical procedures. Objective: 1) To identify effects of surgical stress on cytokine levels in ACS, 2) identify haematological markers for prediction of cytokine production in ACS and 3) investigate the necessity for specialised ACS containers when preparing a cytokine-rich serum. Methods: Experimental in vitro study. Methods: Blood was drawn from 15 stallions admitted for elective castration preoperatively and 22-24 h post operatively and incubated in A...
Treiber K, Carter R, Gay L, Williams C, Geor R.Inflammatory and redox signals could render lamellar tissue susceptible to damage and contribute to higher risk for laminitis in obese or insulin resistant ponies just as these factors contribute to health risks in humans with metabolic syndrome. This study evaluated circulating markers of inflammatory and redox status in ponies that had a history of recurrent bouts of pasture-associated laminitis (PL, n = 42) or had never developed clinical laminitis (NL, n = 34) under the current management conditions. There were no differences (P > 0.05) between PL and NL ponies for markers of antioxidan...
Paillot R, Darby AC, Robinson C, Wright NL, Steward KF, Anderson E, Webb K, Holden MT, Efstratiou A, Broughton K, Jolley KA, Priestnall SL....The acquisition of superantigen-encoding genes by Streptococcus pyogenes has been associated with increased morbidity and mortality in humans, and the gain of four superantigens by Streptococcus equi is linked to the evolution of this host-restricted pathogen from an ancestral strain of the opportunistic pathogen Streptococcus equi subsp. zooepidemicus. A recent study determined that the culture supernatants of several S. equi subsp. zooepidemicus strains possessed mitogenic activity but lacked known superantigen-encoding genes. Here, we report the identification and activities of three novel ...
van den Boom R, Brama PA, Kiers GH, DeGroot J, Barneveld A, van Weeren RR.Matrix metalloproteinases (MMPs) and tumour necrosis factor alpha (TNF-alpha) may be useful as biomarkers of joint disease or inflammation. However, activity of both MMPs and TNF-alpha in synovial fluid (SF) may be influenced by nonpathological factors such as arthrocentesis or exercise. Objective: To investigate the influence of repeated arthrocentesis and exercise on MMP and TNF-alpha activities in SF from normal equine joints. Methods: SF was collected from the left metacarpophalangeal, radiocarpal and tarsocrural joints of 16 horses. Eight of these horses were subsequently subjected to an ...
Frellstedt L, Waldschmidt I, Gosset P, Desmet C, Pirottin D, Bureau F, Farnir F, Franck T, Dupuis-Tricaud MC, Lekeux P, Art T.In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs) and costimulatory and antigen-presenting molecules. Lower airway diseases are also a common problem in sport and racing horses. Because innate immunity plays an essential role in lung defense mechanisms, we assessed the effect of acute exercise and training on innate immune responses in two different compartments. Blood monocytes and pulmonary alveolar macrophages (PAMs) were collected from horses in untrained, moderately trained, inten...
McFarlane D, Holbrook TC.Equine pituitary pars intermedia dysfunction (PPID) is the result of a loss of dopaminergic inhibition of the pars intermedia secondary to neurodegeneration of periventricular hypothalamic neurons. The pathologic events contributing to development of neurodegeneration or clinical signs in equids with PPID are unknown. Chronic inflammation may contribute to initiation or progression of PPID. Objective: Horses with PPID have a distinct systemic cytokine profile compared with that of normal adult or aged horses. The cytokine profile of healthy aged horses differs from that of adult horses. Method...
Moraes AP, Moreira JJ, Brossi PM, Machado TS, Michelacci YM, Baccarin RY.This study aimed to verify whether transient inflammatory reactions incited by the administration of intra-articular platelet-rich plasma (PRP) affected joint components through short- and long-term in vivo evaluation of inflammatory biomarkers and extracellular matrix degradation products in synovial fluid. The effects of PRP were analyzed in a short phase protocol (SPP) and in a prolonged phase protocol (PPP), using saline-injected joints as controls. In the SPP, higher white blood cell counts and prostaglandin E2 and total protein concentrations were observed in the synovial fluid of PRP-tr...
Lankveld DP, Bull S, Van Dijk P, Fink-Gremmels J, Hellebrekers LJ.Ketamine is widely used in equine anaesthesia. Beside its anaesthetic and analgesic properties, ketamine possesses a cytokine-modulating activity. However, to date, no data are available regarding the inhibitory effect of ketamine on the cytokine response in horses. In horses, cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) play a pivotal role in the pathogenesis of equine endotoxaemia following gastrointestinal disorders. Hence, the objective of this study was to assess the influence of ketamine on LPS-induced TNF-alpha and IL-6 formation in an equine macro...
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...
Cudmore LA, Muurlink T, Whittem T, Bailey SR.Pro-inflammatory cytokines, such as IL-1β and TNFα, play a major role in activating leukocytes and endothelial cells during the systemic inflammatory response to endotoxin in the horse. β2 agonist drugs, such as clenbuterol, inhibit leukocyte activation. This study aimed to determine the effects of oral clenbuterol on clinical and leukocyte responses, including production of TNFα, in an in vivo endotoxin challenge model. In a randomised crossover design, horses received either clenbuterol or a placebo product prior to the administration of low dose endotoxin (30 ng/kg over 30 min). Clinica...
Watkins A, Fasanello D, Stefanovski D, Schurer S, Caracappa K, D'Agostino A, Costello E, Freer H, Rollins A, Read C, Su J, Colville M, Paszek M....Lameness is a debilitating condition in equine athletes that leads to more performance limitation and loss of use than any other medical condition. There are a limited number of non-terminal experimental models that can be used to study early inflammatory and synovial fluid biophysical changes that occur in the equine joint. Here, we compare the well-established carpal IL-1β-induced synovitis model to a tarsal intra-articular lavage model, focusing on serial changes in synovial fluid inflammatory cytokines/chemokines and the synovial fluid lubricating molecules lubricin/proteoglycan 4 and hya...
Bamford NJ, Potter SJ, Harris PA, Bailey SR.The relative influences of obesity and adaptation to high glycaemic diets on the development of insulin dysregulation in equids are unclear. Objective: To determine whether increased adiposity per se is responsible for the decreased insulin sensitivity often observed in obese horses or whether a dietary glycaemic response is critically important. Methods: Randomised controlled trial. Methods: Eighteen horses and ponies were studied over a 20-week period. They received ad libitum hay plus either a high fat (low glycaemic) diet (FAT; n = 6) or a similar (isocaloric) diet containing 1.5 g/kg bwt ...
Galvão A, Henriques S, Pestka D, Lukasik K, Skarzynski D, Mateus LM, Ferreira-Dias GM.We hypothesized that cytokines influence luteal angiogenesis in mares, while angiogenic factors themselves can also regulate luteal secretory capacity. Therefore, the purpose of this study was to evaluate the role of cytokines--tumor necrosis factor alpha (TNF), interferon gamma (IFNG) and Fas ligand (FASL)--on in vitro modulation of angiogenic activity and mRNA level of vascular endothelial growth factor A (VEGF), its receptor VEGFR2, thrombospondin 1 (TSP1), and its receptor CD36 in equine corpus luteum (CL) throughout the luteal phase. After treatment, VEGF protein expression was determined...
Little CB, Flannery CR, Hughes CE, Goodship A, Caterson B.To determine whether the focal susceptibility to cartilage degeneration in joints is related to a differential response to cytokine stimulation. Methods: Compare aggrecan and collagen catabolism in in-vitro models of cartilage degradation induced by retinoic acid (RA), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF) and IL-1 plus oncostatin M (OSM). Glycosaminoglycan (GAG) and hydroxyproline (HyPro) quantification and Western immunoblot analyses of aggrecan and collagen degradation products were undertaken in explant cultures of normal cartilage from regions of equine joints with a kno...
Barton MH, Collatos C.The purpose of this study was to evaluate the diagnostic and prognostic significance of tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) activities and endotoxin concentration in blood and peritoneal fluid of 155 adult horses with acute abdominal disease (colic). Samples also were obtained from 20 healthy adult horses. Blood and peritoneal fluid supernatant TNF and IL-6 activities and endotoxin concentration were significantly greater in horses with colic, compared with healthy horses. In horses with colic, the peritoneal fluid endotoxin concentration and TNF and IL-6 activities were...
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...
