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Topic:Inflammation
Inflammation is a biological response of the horse's body to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a complex process that involves the activation of immune cells, the release of inflammatory mediators, and changes in blood flow. In horses, inflammation can manifest in various forms, affecting different tissues and organs, including the joints, respiratory system, and skin. The inflammatory response is an essential component of the horse's immune system, aiming to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and establish tissue repair. This topic page gathers peer-reviewed research studies and scholarly articles that explore the mechanisms, effects, and management of inflammation in equine health.
Ocular immunology in equine recurrent uveitis. Equine recurrent uveitis (ERU) is a disease with high prevalence and relevance for the equine population, since it results in blindness. Over the last decade, important advancements have been made in our understanding of the underlying immune responses in this disease. ERU is mediated by an autoaggressive Th1 response directed against several retinal proteins. Interphotoreceptor-retinoid binding protein (IRBP) and cellular retinaldehyde-binding protein (CRALBP) are capable to induce ERU-like disease in experimental horses, with the unique possibility to activate relapses in a well-defined mann...
The effect of lidocaine on in vitro adhesion and migration of equine neutrophils. The effect of lidocaine on in vitro migration and adhesion of equine neutrophils was evaluated. Neutrophils were isolated from equine whole blood using a Percoll-gradient centrifugation protocol. Purified neutrophils were incubated with lidocaine at concentrations from 0.1 to 1000 microg/ml for 30 min at 37 degrees C, after calcein loading. Neutrophil integrin-mediated adhesion in response to stimulation with 100 nM LTB(4), 100 nM PAF, or 100 ng/ml IL-8, or integrin-mediated migration in response to stimulation with 100 nM LTB(4), 150 nM PAF, or 100 ng/ml IL-8 was assessed. Statistical signifi...
Evaluation of four topical preparations for the treatment of cannon hyperkeratosis in a horse. The response to treatment with four topical preparations was evaluated in an 11-year-old Morgan horse mare with histologically confirmed quadrilateral cannon hyperkeratosis. Each limb was treated for 30 days with 0.1% tacrolimus ointment, 0.1% adapalene gel, 0.2% phytosphingosine spray or a water-based emollient. Response to treatment was evaluated both histologically and visually. A water-based emollient and 0.1% tacrolimus ointment produced encouraging clinical responses. Pre-treatment histopathology identified marked, mostly compact, hyperkeratosis and follicular hyperkeratosis, most promin...
Serial gastrointestinal ultrasonography following exploratory celiotomy in normal adult ponies. The objective was to characterize ultrasonographic changes in bowel wall thickness, contractility, degree of distension, luminal contents, and peritoneal fluid associated with exploratory celiotomy in normal ponies. Gastrointestinal ultrasonographic examination was performed in 14 ponies on days 1, 3, 5, and 7 after an exploratory celiotomy. Wall thickness, contractility, degree of distension, and luminal contents were recorded for the duodenum and jejunum. Stomach wall thickness and location, cecal wall thickness, and peritoneal fluid location and character were recorded. Peritoneal fluid was...
Anti-inflammatory and analgesic effects of intra-articular injection of triamcinolone acetonide, mepivacaine hydrochloride, or both on lipopolysaccharide-induced lameness in horses. To assess analgesia, inflammation, potency, and duration of action associated with intra-articular injection of triamcinolone acetonide (TA), mepivacaine hydrochloride, or both in metacarpophalangeal (MCP) joints of horses with experimentally induced acute synovitis. Methods: 18 horses. Methods: Both forelimbs of each horse were injected with lipopolysaccharide (LPS) 3 times. After the first LPS injection, 1 forelimb of each horse was treated with intra-articular injection of mepivacaine (80 mg; n=6), TA (9 mg; 6), or mepivacaine with TA (same doses of each; 6) 12 hours after the initial LPS i...
Basal and stimulus-induced cytokine expression is selectively impaired in peripheral blood mononuclear cells of newborn foals. Neonates are thought to be generally deficient in production of Th-1-associated cytokines at birth, and thereby more susceptible to bacterial infections. Using neonatal foals as a model, this study examined the age-dependent maturation of both basal and stimulus-induced immune responses, as reflected by the expression of a panel of Th-1-associated and pro-inflammatory cytokines. Results showed that although the basal production of IFN-gamma and IL-6 was impaired (P<0.05) in PBMCs of neonatal foals at birth, the basal production of IL-8, IL-12(p35/p40) and IL-23(p19/p40) were either in exces...
Matrix metalloproteinases in inflammatory pathologies of the horse. The extracellular matrix (ECM) of connective tissue is constantly being remodelled to allow for growth and regeneration. Normal tissue maintenance requires the ECM components to be degraded and re-synthesised in relatively equal proportions. This degradation is facilitated by matrix metalloproteinases (MMPs) and their proteolytic action is controlled primarily by the tissue inhibitors of metalloproteinases (TIMPs). Both MMPs and TIMPs exist in a state of dynamic equilibrium, with a slight excess of one or the other depending on the need for either ECM breakdown or synthesis. Long-term disrupti...
Treatment of oromaxillary fistulae in nine standing horses (2002-2006). There is minimal published information on equine oromaxillary fistulae that are unrelated to cheek teeth (CT) repulsion or on the conservative treatment of these atypical fistulae. Objective: To report equine oromaxillary fistulae unrelated to CT extraction and describe their management in standing horses. Methods: Case details of oromaxillary fistulae of atypical aetiology occurring at 2 referral centres between 2002-2006, including their treatment and response to treatment were examined. Results: Nine cases of oromaxillary fistula were recorded, mainly in aged horses (median 22 years). Fistu...
Effects of a MAPK p38 inhibitor on lung function and airway inflammation in equine recurrent airway obstruction. It has been suggested that many of the beneficial effects of corticosteroids are mediated through mitogen-activated protein kinase (MAPK) p38 inhibition. Objective: To investigate the efficacy of the MAPK p38 inhibitor compound MRL-EQ1 to either prevent (Phase 1) or treat (Phase 2) recurrent airway obstruction (RAO) in horses. Methods: MRL-EQ1 was administered i.v. at a dosage of 0.75-1.5 mg/kg bwt q. 12 h. In Phase 1, susceptible horses in clinical remission were divided into 2 groups (n = 5/group), based on historical values of respiratory mechanics. All horses were entered in the study in p...
Cloning and expression of ADAM-related metalloproteases in equine laminitis. Equine laminitis is a debilitating disease affecting the digital laminae that suspend the distal phalanx within the hoof. While the clinical progression of the disease has been well documented, the molecular events associated with its pathogenesis remain largely unknown. Using real time quantitative PCR (RT-qPCR), we have investigated the expression of genes coding for proteins containing a Disintegrin and Metalloprotease domain (ADAM), as well as genes encoding the natural inhibitors of these enzymes (tissue inhibitor of metalloprotease; TIMP) in horses with naturally-acquired (acute, chronic...
Equine odontoclastic tooth resorption and hypercementosis. A poorly described, painful disorder of incisor and canine teeth, variably causing periodontitis, with resorptive or proliferative changes of the calcified dental tissues, has recently been documented in aged horses. No plausible aetiopathogenesis for this syndrome has been recorded. Eighteen diseased teeth from eight horses were examined grossly and microscopically and showed the presence of odontoclastic cells by tartrate resistant acid phosphatase (TRAP) staining. A chronological sequence of odontoclastic resorption followed by hypercementosis was demonstrated and, consequently, the term eq...
Liposome-based diclofenac for the treatment of inflammation in an acute synovitis model in horses. Lameness as a result of joint disease is a major source of decreased athletic performance in the horse. Most treatment protocols include the administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Phenylbutazone, alone or in combination with other treatments, is the most commonly and widely used NSAID, however it has the potential for serious side effects. The introduction of the liposome-based formulation of the NSAID diclofenac has shown promising effect as a safe and convenient treatment for lameness associated with osteoarthritis. The purpose of this study was to evaluate the effe...
The role of leukocyte biology in laminitis. The underlying pathogenesis of laminitis clearly depends importantly on inflammatory processes that recruit leukocytes at an early stage in disease. The role of leukocytes in the initiation of laminitis, or as an intermediary factor is currently being investigated using a limited array of models, and future studies require both new reagent and model systems if we are to clearly define how leukocytes propagate this disease. The opportunities presented by this type of research could easily include new and powerful treatment and preventative modalities.
Sepsis-From human organ failure to laminar failure. The horse with gram negative sepsis is known to be at particular risk of succumbing to laminitis. This review summarizes recent evidence indicating that similar pathologic events relating to inflammatory injury occur in laminar failure in laminitis as occur in organ injury/failure in human sepsis. The discussion also points out some important differences between the laminae and target organs in human sepsis that impact the clinical nature of the disease.
Tissue concentrations of 4-HNE in the black walnut extract model of laminitis: indication of oxidant stress in affected laminae. In the septic horse prone to laminitis, a similar activation of the innate immune system appears to occur as reported in the septic human prone to organ failure. Because oxidant injury plays a central role in organ failure occurring due to an overzealous innate immune response in human sepsis, this study was performed to determine whether there was evidence of oxidant stress in the laminar tissue in the early stages of laminitis. 4-Hydroxy-2-nonenal (4-HNE), a lipid aldehyde that forms due to lipid peroxidation occurring during episodes of oxidant stress, readily forms adducts with cellular pr...
Metabolic syndrome-From human organ disease to laminar failure in equids. Obesity, insulin resistance, hyperinsulinemia and hypertriglyceridemia are components of an equine metabolic syndrome phenotype associated with increased laminitis risk in horses. Links between these conditions and laminitis must still be elucidated, but human medicine provides candidate mechanisms for future study, including inflammation associated with obesity, vascular compromise induced by insulin resistance, and endothelial dysfunction. Just as metabolic syndrome has been linked to cardiovascular disease in humans, studies are now required to determine the exact mechanisms responsible for...
Equine laminitis: a journey to the dark side of venous. Equine laminitis is a crippling condition that continues to defy repeated efforts to delineate the precise mechanisms involved and develop effective therapeutic strategies for use in the clinic. In this article, the possible role of dysfunction of the laminar vasculature is discussed, with particular emphasis on the venous side of the laminar microvasculature and the possible role(s) that metabolic syndrome and thrombosis may play in the dysfunction observed in the laminar microvasculature during the development of laminitis.
Thromboxane and isoprostanes as inflammatory and vasoactive mediators in black walnut heartwood extract induced equine laminitis. Inflammation and vascular dysfunction occur concurrently during the prodromal stages of equine laminitis. The aim of this study was to provide insights into the role that thromboxane and isoprostanes may play in the development of black walnut heartwood extract (BWHE)-induced laminitis. Horses were divided into two groups, either control or BWHE-administered horses. Plasma concentrations of thromboxane increased transiently after administration of BWHE and coincided with the nadir in white blood cell counts, whereas plasma concentrations of iso-prostaglandin PGF(2alpha) (iso-PGF(2alpha)) did n...
Extracellular matrix, leukocyte migration and laminitis. The structure and dynamic nature of extracellular matrix is discussed in the context of healthy and diseased tissues particularly the equine digital laminae.
Role of p38 MAPK in LPS induced pro-inflammatory cytokine and chemokine gene expression in equine leukocytes. Endotoxemia occurs when bacterial lipopolysaccharide (LPS) in the blood induces a dysregulated inflammatory response, resulting in circulatory shock and multi-organ failure. Laminitis is a common complication in endotoxemic horses and is frequently the reason for humane euthanasia of these cases. Blood leukocytes are a principal target of LPS in endotoxemia leading to activation of multiple signal transduction pathways involved in the induction of a number of pro-inflammatory genes. In other animal models, the p38 mitogen activated protein kinase (MAPK) pathway has been associated with induced...
p38 mitogen-activated kinase (MAPK) is essential for equine neutrophil migration. Equine laminar tissues do not contain resident neutrophils and have less superoxide dismutase (SOD) activity than other equine tissues, which makes them inherently more vulnerable to damage induced by reactive oxygen species (ROS) produced by neutrophils that enter the tissues. In the advanced clinical stages of acute laminitis, pathologic events in affected feet include a breakdown in the basement membrane, neutrophil infiltration, and platelet-neutrophil aggregates in laminar dermal veins, highlighting the contribution of neutrophils to the pathophysiology of the disease. The aim of this stu...
Indices of inflammation in the lung and liver in the early stages of the black walnut extract model of equine laminitis. The liver and lung are not only described as "target organs" in sepsis in most species, but are purported to be sources of circulating inflammatory mediators central to the systemic inflammatory response syndrome (SIRS). As we have recently reported an inflammatory response in the laminar tissue in laminitis similar to that described in "target organs" in human sepsis, we investigated the inflammatory response of the lung and liver in the black walnut extract (BWE) model of equine laminitis to determine (1) if a similar systemic inflammatory response occurs in this laminitis model as described...
Temporal aspects of laminar gene expression during the developmental stages of equine laminitis. The results of recent studies indicate that inflammatory responses occurring in the early stages of equine laminitis lead to downstream events that eventually result in failure of the bond between the hoof wall and the distal phalanx. In order to gain further insights into the molecular mechanisms involved in the development of laminitis, an equine-specific cDNA microarray consisting of transcripts for more that 3000 genes was used to assess temporal changes in gene expression in laminar tissues at 1.5, 3 and 12 h after administration of either a laminitis-inducing agent (black walnut heartwoo...
The effect of methyl sulphonyl methane supplementation on biomarkers of oxidative stress in sport horses following jumping exercise. Exercise induces changes in several organs and tissues, and this process might be due to oxidative damage caused by free radicals and inflammatory mediators. Methyl Sulphonyl Methane, better known as MSM, is a naturally occurring sulphur compound with well-known antioxidant properties. On the other hand, Vitamin C is important in limiting free radical damage in the aqueous phase of the cell, and cellular vitamin C status may be linked to the mechanisms involved in quenching cellular reactive oxygen species. The aim of this study was to determine if supplementation with MSM and vitamin C could ...
Plasma concentrations of endotoxin and platelet activation in the developmental stage of oligofructose-induced laminitis. The link between the fermentation of carbohydrate in the equine large intestine and the development of acute laminitis is poorly understood. Absorption of endotoxin (lipopolysaccharide; LPS) into the plasma has been observed in one experimental model of laminitis, but does not cause laminitis when administered alone. Thus, the potential role of endotoxin is unclear. Platelet activation has previously been demonstrated in the developmental stage of laminitis. Equine platelets are more sensitive than leukocytes to activation by endotoxin, and can be activated directly by LPS in the low pg/ml ran...
Endotoxin-induced activation of equine digital vein endothelial cells: role of p38 MAPK. The endothelium plays a major role in the pathogenesis of endotoxemia. Binding of endotoxin (lipopolysaccharide; LPS) to endothelium initiates a range of signalling events, including activation of p38 mitogen activated protein kinases (MAPKs) that are involved in the initiation of inflammatory responses. In the present study we have examined whether clinically relevant concentrations of LPS can activate p38 MAPK in equine endothelial cells and have investigated the role of the kinase in neutrophil adhesion and mediator release. Cultured equine digital vein endothelial cells (EDVEC) were expose...
Inflammatory and redox status of ponies with a history of pasture-associated laminitis. 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...
Leukocyte-derived and endogenous matrix metalloproteinases in the lamellae of horses with naturally acquired and experimentally induced laminitis. Inflammation and dysregulation of endogenous matrix metalloproteinase (MMP) production are implicated in the development of equine laminitis. In this study, we examine quantitative relationships among levels of leukocyte-derived proMMP-9 and MMP-9, lamellar proMMP-2 and MMP-2, and expression of proMMP-2 processing enzymes, MT1-MMP/PACE4, as steps towards determining whether inflammation and dysregulation of endogenous MMP production are independent or co-dependent processes. Methods: Archived samples of lamellae from horses with naturally acquired laminitis (n = 12), and from horses administer...
Pathophysiologic effects of phenylbutazone on the right dorsal colon in horses. To determine pathophysiologic effects of phenylbutazone on the equine right dorsal colon (RDC). Methods: 12 healthy adult horses. Methods: A controlled crossover observational study was conducted. Clinical and serum variables, colonic inflammation (histologic grading), and measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA) and prostaglandin E(2) (PGE(2)) concentrations, ingesta volatile fatty acid (VFA) content, and arterial blood flow in the RDC were evaluated for a 21-day period in horses administered phenylbutazone (8.8 mg/kg, PO, q 24 h) or a control substance. Results: D...
Effect of body condition, body weight and adiposity on inflammatory cytokine responses in old horses. 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...
