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Topic:Inflammatory Response
The inflammatory response in horses is a complex physiological process that occurs when the immune system reacts to harmful stimuli such as pathogens, damaged cells, or irritants. This response is characterized by the activation of various immune cells, the release of signaling molecules, and the production of inflammatory mediators. In horses, the inflammatory response involves both innate and adaptive immune mechanisms, which work together to eliminate the source of harm and initiate tissue repair. Key components of the equine inflammatory response include cytokines, chemokines, and leukocytes, which coordinate the body's defense and healing processes. This page gathers peer-reviewed research studies and scholarly articles that explore the mechanisms, regulation, and implications of the inflammatory response in equine health and disease.
Neutrophil NETs in reproduction: from infertility to preeclampsia and the possibility of fetal loss. The intention of this review is to provide an overview of the potential role of neutrophil extracellular traps (NETs) in mammalian reproduction. Neutrophil NETs appear to be involved in various stages of the reproductive cycle, starting with fertility and possibly ending with fetal loss. The first suggestion that NETs may play a role in pregnancy-related disorders was in preeclampsia, where vast numbers were detected in the intervillous space of affected placentae. The induction of NETosis involved an auto-inflammatory component, mediated by the increased release of placental micro-debris in p...
Seasonal differences in cytokine expression in the skin of Shetland ponies suffering from insect bite hypersensitivity. Insect bite hypersensitivity (IBH) in horses is a seasonal, IgE-mediated, pruritic skin disorder primarily caused by Culicoides spp. We hypothesize that a mixed Th2/Th1-type immune status, off season, alters into Th2-dominated immune reactivity in the skin of IBH-affected ponies in the IBH season. To study these immune response patterns Culicoides-specific IgE levels, skin histopathology and cytokine and transcription factor mRNA expression (IL4, IL10, IL13, IFNγ, FoxP3 and CD3(ζ)) in lesional and non-lesional skin of ponies affected by IBH in the IBH season were compared with those of the s...
Characterization of the inflammatory infiltrate and cytokine expression in the skin of horses with recurrent urticaria. Recurrent urticaria (RU) is a common skin disease of horses, but little is known about its pathogenesis. Objective: The aim of this study was to characterize the inflammatory cell infiltrate and cytokine expression pattern in the skin of horses with RU. Methods: Biopsies of lesional and nonlesional skin of horses with RU (n = 8) and of skin from healthy control horses (n = 8) were evaluated. Methods: The inflammatory cell infiltrate was analysed by routine histology. Immunohistochemistry was used to identify T cells (CD3), B ells (CD79), macrophages (MAC387) and mast cells (tryptase). E...
Equine myeloperoxidase: a novel biomarker in synovial fluid for the diagnosis of infection. Equine joint infection is a life-threatening disorder, and confirmation of the diagnosis can be difficult. Synovial fluid biomarkers may assist the discrimination between infectious and noninfectious joint disease. Objective: This study investigates whether the immunological detection of total and enzymatically active myeloperoxidase (MPO) assists the diagnosis of joint infection in horses. Methods: The following 4 sample groups were included: healthy; osteochondritis dissecans (OCD); traumatic synovitis; and culture-confirmed infected joints. Synovial fluid was analysed for total MPO by a hor...
Progestin treatment does not affect expression of cytokines, steroid receptors, oxytocin receptor, and cyclooxygenase 2 in fetal membranes and endometrium from pony mares at parturition. In most mammalian species, progestins have a major function in maintaining pregnancy. In humans, the physiologic initiation of parturition bears similarities with inflammatory processes and anti-inflammatory effects of progestins have been suggested to postpone birth until term. To examine if comparable effects exist in the horse, mares were treated with the synthetic progestin altrenogest from day 280 of gestation until parturition (N = 5) or were left untreated as controls (N = 7). Tissue from the amnion (AMN), allantochorion (AC), and endometrium (EM) was collected at foaling and mRNA expre...
The effect of intravenous lidocaine infusion on bronchoalveolar lavage cytology in equine recurrent airway obstruction. Lidocaine decreases neutrophilic inflammation in models of acute lung injury and decreases inflammation in asthmatic patients. Neutrophilic bronchiolitis develops in recurrent airway obstruction (RAO), but it remains unknown if lidocaine infusion decreases neutrophil migration into the airways. Objective: Lidocaine decreases neutrophilic inflammation as measured in BALF in RAO-affected horses. Methods: Six RAO-susceptible horses in remission. Methods: In a randomized cross-over design, horses received lactated Ringer's solution (LRS) IV or lidocaine hydrochloride IV with a minimum of 4 weeks a...
Optimization of leukocyte concentration in platelet-rich plasma for the treatment of tendinopathy. Numerous methods are available for platelet-rich plasma (PRP) generation, but evidence defining the optimum composition is lacking. We hypothesized that leukocyte-reduced PRP would result in lower inflammatory cytokine expression compared with concentrated-leukocyte PRP and that maintaining the platelet:white blood cell (WBC) ratio would compensate for the effect of increased WBC concentration. Methods: Blood and flexor digitorum superficialis tendons were collected from young adult horses. Three PRP groups were generated with the same platelet concentration but different WBC concentrations: i...
Gene profiling of inflammatory genes in day 18 endometria from pregnant and non-pregnant mares. Maternal recognition of pregnancy is a physiological process that primarily describes endometrial responses to a conceptus. Recognition of a conceptus prevents the release of prostaglandin F(2α) , thereby ensuring survival of the corpus luteum and continued progesterone production. Exactly how this occurs in the mare is poorly understood. Because prostaglandin F(2α) is a pro-inflammatory hormone, we hypothesized that differential gene expression in the endometrium at the time of maternal recognition reflects an anti-inflammatory event leading to decreased prostaglandin F(2α) secretion. Mare...
An in vitro whole blood model to test the effects of different stimuli conditions on the release of myeloperoxidase and elastase by equine neutrophils. Horses are particularly sensitive and exposed to excessive inflammatory responses evolving toward an important stimulation of polymorphonuclear neutrophils (PMNs). The aim of this work was to stimulate equine neutrophils in whole blood and to evaluate their response by measuring the release of total and active myeloperoxidase (MPO) and total elastase, considered as markers of neutrophil stimulation and degranulation. Because of the critical importance of the concomitant presence of LPS and TNF-α in equine pathological situations, we combined these two natural mediators to stimulate PMN and co...
Effect of training status on immune defence related gene expression in Thoroughbred: are genes ready for the sprint? Athletic performance is both a stress factor and an adaptive response to exercise that may be modulated by training, reduce inflammation and help prevent disease. Studies on the endocrinology of exercise and training have demonstrated the existence of an integrated metabolic network of hormone and cytokine regulation. Subsequent molecular studies have shown that repeated bouts of exercise may establish new basal levels of gene expression at rest. The Thoroughbred horse may be a useful 'exercise model' for inter-individual comparisons between subjects with homogeneous genetic and environmental ...
Effects of a “two-hit” model of organ damage on the systemic inflammatory response and development of laminitis in horses. The role of endotoxemia in the development of laminitis remains unclear. Although systemic inflammation is a risk factor for laminitis in hospitalized horses, experimental endotoxin administration fails to induce the disease. While not sufficient to cause laminitis by itself, endotoxemia might predispose laminar tissue to damage from other mediators during systemic inflammation. In "two-hit" models of organ damage, sequential exposure to inflammatory stimuli primes the immune system and causes exaggerated inflammatory responses during sepsis. Acute laminitis shares many characteristics with se...
Ethyl pyruvate diminishes the inflammatory response to lipopolysaccharide infusion in horses. 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...
Expression of interleukin-1β, interleukin-8, and interferon-γ in blood samples obtained from healthy and sick neonatal foals. To evaluate and compare the gene expression of interleukin(IL)-1β, IL-8, and interferon-γ during the first 72 hours after birth in healthy foals and during the first 72 hours after hospitalization in sick neonatal foals and investigate correlations of clinicopathologic variables with cytokine expressions in healthy and sick neonatal foals. Methods: 33 foals < 7 days old (10 healthy foals, 7 foals with sepsis, 6 foals with peripartum asphyxia syndrome, and 12 foals with other diseases [2 with failure of passive transfer of immunity only were not further evaluated]). Methods: A blood sample...
Post-mating inflammatory responses of the uterus. This review attempts to summarize the current knowledge on uterine inflammatory response after mating in horses, pigs and cattle. Post-mating endometritis has been extensively studied in horses as it has been considered to cause infertility. The inflammation is known to occur also in cattle, but it has not been investigated to a similar extent. There are a number of publications about mechanisms of post-mating uterine inflammation in pigs, which seem to resemble those in horses. The major focus of this review is the horse, but relevant literature is presented also on swine and cattle. Spermato...
Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses. To determine whether the method of lipopolysaccharide (LPS) administration (intermittent vs continuous) affects the magnitude and duration of the systemic inflammatory response in horses and whether prolonged (48 hours) endotoxemia induces laminitis. Methods: 12 healthy adult horses (10 mares and 2 geldings). Methods: Horses were randomly assigned to receive LPS (total dose, 80 μg; n = 4) or saline (0.9% NaCl) solution (80 mL/h; 4) via constant rate infusion or 8 bolus IV injections of LPS (10 μg, q 6 h;4) during a 48-hour period. Physical examinations were performed every 4 hours, inflammat...
Markers of systemic inflammation in horses with heaves. Systemic inflammation in horses with heaves is poorly characterized. Objective: To assess acute phase proteins (APP) and inflammatory cytokine profiles in serum of healthy horses and horses with heaves. Methods: Six healthy horses and 6 heaves-affected horses belonging to the University of Montreal. Methods: Prospective, observational study. Healthy and heaves-affected control horses were exposed to a 30-day natural challenge with hay and straw to induce clinical exacerbation of heaves. Serum samples were obtained by venipuncture before (T0) as well as after 7 (T7) and 30 days (T30) of stablin...
Evaluation of the inflammatory response in experimentally induced synovitis in the horse: a comparison of recombinant equine interleukin 1 beta and lipopolysaccharide. To compare two transient models of synovitis-osteoarthritis (OA) in horses by characterizing biological changes in synovial fluid and joint tissue. Methods: Twelve skeletally mature mares were utilized in a block design. Synovitis was induced by an intra-articular injection of 100 ng recombinant equine interleukin 1 beta (reIL-1β) or 0.5 ng lipopolysaccharide (LPS) into a middle carpal joint in 1 ml volumes. One ml of saline was injected into the contra-lateral control joint. Lameness evaluations were conducted through post-injection hour (PIH) 8 (at which time arthroscopic removal of syno...
Effects of age and R848 stimulation on expression of Toll-like receptor 8 mRNA by foal neutrophils. The innate immune system plays a critical role in protecting neonates against infections early in life and Toll-like receptors (TLRs) are key components of innate immune recognition of pathogens. This study examined the effects of age and stimulation with a TLR 7/8 agonist (R848) on TLR8 mRNA expression by foal neutrophils during the first month of life. We also examined the effects of R848 stimulation on mRNA expression of interleukin (IL)-6 and IL-8 at 1 and 14 days of life. We observed that TLR8 mRNA was constitutively expressed (P<0.05) at all ages examined, and its expression did not c...
Effects of oral treatment with N-acetylcysteine on the viscosity of intrauterine mucus and endometrial function in estrous mares. Persistent breeding-induced endometritis is ranked as the third most common medical problem in the adult mare and leads to enormous economic loss in horse breeding. In mares suffering from persistent breeding-induced endometritis, increased amounts of intrauterine (i.u.) fluid or viscous mucus in estrus or after breeding may act as a barrier for sperm and can contribute to low fertility. Current therapies of these mares aim to eliminate i.u. fluid and mucus by uterine lavage and/or administration of ecbolic drugs. Recently, i.u. administration of N-acetylcysteine (NAC) has been shown to suppor...
Laminar regulation of STAT1 and STAT3 in black walnut extract and carbohydrate overload induced models of laminitis. STAT1 and STAT3 are important signaling molecules in disorders of systemic inflammation and are likely to be involved in laminitis, as laminar and systemic inflammation have been well documented in experimental models of laminitis. Objective: The STAT1 and STAT3 activation (via phosphorylation of tyrosine and serine moieties) is occurring in the laminar tissue during the developmental and onset of lameness time points in both the black walnut extract (BWE) and carbohydrate overload (CHO) models of laminitis. Methods: Archived laminar tissue from horses. Methods: Experimental studies of induced...
Label-free LC-MSMS analysis of vitreous from autoimmune uveitis reveals a significant decrease in secreted Wnt signalling inhibitors DKK3 and SFRP2. Equine recurrent uveitis is a severe and frequent blinding disease in horses which presents with auto-reactive invading T-cells, resulting in the destruction of the inner eye. Infiltration of inflammatory cells into the retina and vitreous is driven by currently unknown guidance cues, however surgical removal of the vitreous (vitrectomy) has proven therapeutically successful. Therefore, proteomic analyses of vitrectomy samples are likely to result in detection of proteins contributing to disease pathogenesis. Vitreous from healthy and ERU diseased horses were directly compared by quantitative ...
Pattern recognition receptors in equine endotoxaemia and sepsis. Pattern recognition receptors (PRRs) on host cells detect pathogens to activate innate immunity which, in turn, initiates inflammatory and adaptive immune responses. Successful activation of PRRs is, therefore, critical to controlling infections and driving pathogen-specific adaptive immunity, but overactivity of PRRs causes systemic inflammation, which is detrimental to the host. Here we review the PRR literature as it relates to horses and speculate on the role PRRs may play in sepsis and endotoxaemia.
Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro. Endotoxemia is responsible for severe illness in horses. Individuals can become clinically unresponsive to the endotoxin molecule after an initial exposure; a phenomenon referred to as 'endotoxin tolerance' (ET). ET has been observed clinically in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMC) in vitro, and to describe selected cytokine responses which are associated with ET. ET was induced by culturing cells with three c...
A Potential Role for Pro-Inflammatory Cytokines in the Development of Insulin Resistance in Horses. Understanding the mechanisms involved in the development of insulin resistance in horses should enable development of effective treatment and prevention strategies. Current knowledge of these mechanisms is based upon research in obese humans and rodents, in which there is evidence that the increased production of pro-inflammatory cytokines by adipose tissue negatively influences insulin signaling in insulin-responsive tissues. In horses, plasma concentrations of the cytokine, tumor necrosis factor-α, have been positively correlated with body fatness and insulin resistance, leading to the hypo...
Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles. Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By analysis of VRP targeting in the draining lymph node, we found that VRP induced rapid recruitment of TNF-s...
Gluten-dependent antibodies in horses with inflammatory small bowel disease (ISBD). Equine inflammatory small bowel disease (ISBD) is an idiopathic pathologic condition seeming to increase in prevalence. Objective: To investigate the potential role of gluten in equine ISBD. Methods: Antibodies known to be important in the diagnosis of human coeliac disease (CD): IgA antibodies to human recombinant and guinea pig tissue-transglutaminase (TGA), native gliadin (AGA), deamidated-gliadin-peptides (DGPA), and primate and equine endomysium (EMA) were assessed in blood samples from three different groups of horses: ISBD affected (n = 12) on a gluten-rich diet and controls either ...
Effect of strenuous exercise and ex vivo TLR3 and TLR4 stimulation on inflammatory gene expression in equine pulmonary leukocytes. The effects of strenuous exercise and ex vivo stimulation of TLR3 and TLR4 pathways on the expression of six inflammatory genes in equine pulmonary leukocytes were investigated. The genes tested were interferon-beta (IFN-β), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), chemokine (c-c motif) ligand 5 (RANTES) and tumor necrosis factor-alpha (TNF-α). We hypothesized that strenuous exercise would modulate basal gene expression on one hand and modulate the response to bacterial lipopolysaccharide (LPS) and to polyinosinic:polycytidylic acid (Pol...
Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis. The objective of the study was to evaluate the gene expression of inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-α, IL-1 receptor antagonist [ra] and serum amyloid A (SAA) in endometrial tissue and circulating leukocytes in response to uterine inoculation of 105 colony forming units (CFU) Escherichia coli in mares. Before inoculation, mares were classified as resistant or susceptible to persistent endometritis based on their uterine inflammatory response to infusion of 109 killed spermatozoa and histological assessment of the endometrial quality. ...
Analgesic and anti-hyperalgesic effects of epidural morphine in an equine LPS-induced acute synovitis model. Epidural morphine is widely used in veterinary medicine, but there is no information about the anti-hyperalgesic and anti-inflammatory effects in acute inflammatory joint disease in horses. The analgesic, anti-hyperalgesic and anti-inflammatory effects of epidural morphine (100mg/animal or 0.17 ± 0.02 mg/kg) were therefore investigated in horses with acute synovitis. In a cross-over study, synovitis was induced in the talocrural joint by intra-articular lipopolysaccharide (LPS). The effect of epidural morphine was evaluated using physiological, kinematic and behavioural variables. Ranges of m...
Cytokine production and proliferation upon in vitro oligodeoxyribonucleotide stimulation of equine peripheral blood mononuclear cells. Synthetic oligodeoxyribonucleotides (ODN) may prove useful immune modulators in equine medicine. It is however important to assess the effects of each specific ODN in the species it is intended to be used in. The present study therefore aimed to evaluate some ODN for induction of cytokine production; i.e. type I interferons (IFN), IFN-γ, tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), and proliferation of equine peripheral blood mononuclear cells (PBMC). A panel of four ODN containing unmethylated cytosine-guanosine sequences (CpG) was used: ODN 1 and ODN 8 repre...
