Endotoxins are components of the outer membrane of Gram-negative bacteria that can have significant effects on horses when they enter the bloodstream. These molecules are known to trigger inflammatory responses in equine systems, leading to conditions such as endotoxemia, which can affect various physiological functions. Research on endotoxins in horses focuses on understanding their impact on equine health, the mechanisms of endotoxin-induced inflammation, and the potential therapeutic interventions. This page includes peer-reviewed research studies and scholarly articles that explore the biological effects, detection methods, and management strategies related to endotoxin exposure in horses.
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...
Ziegler AL, Freeman CK, Fogle CA, Burke MJ, Davis JL, Cook VL, Southwood LL, Blikslager AT.Small intestinal strangulating obstruction (SISO) is associated with endotoxaemia which leads to an increased risk of death. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat signs of endotoxaemia by inhibiting cyclo-oxygenases (COX). COX-1 is expressed constitutively and promotes gut barrier function, whereas COX-2 is inducible and contributes to the signs of endotoxaemia. In preclinical SISO trials, intestinal barrier recovery was more complete with reductions in endotoxin permeability in horses treated with COX-2 selective NSAIDs as compared with horses treated with flunixin m...
Ivester KM, Couëtil LL, Moore GE.Mild equine asthma is presumed to arise in response to environmental exposures but the relative impact of differing inflammatory phenotypes upon performance are largely unexplored. Objective: Airway inflammation negatively affects performance and cytological phenotype varies with environmental exposure. Methods: Thoroughbred racehorses in active training and racing. Methods: Thoroughbreds were recruited 24-48 hours before racing. Each horse was eligible for re-enrollment with each race entry. Within one hour of race completion, physical examination, respiratory endoscopy, and BAL were performe...
Patan-Zugaj B, Gauff FC, Egerbacher M, Licka TF.OBJECTIVE To investigate the effect of lipopolysaccharide (LPS) on type VII collagen- cleaving matrix metalloproteinases (MMPs) in the lamellar tissue of extracorporeally perfused equine limbs. SAMPLE 10 right forelimbs and 3 left forelimbs collected from 10 adult horses after slaughter at a licensed abattoir. PROCEDURES Extracorporeal perfusion of the isolated equine limbs was performed for 10 hours under physiologic conditions (control-perfused limbs; n = 5) and with the addition of 80 ng of LPS/L of perfusate (LPS-perfused limbs; 5). Lamellar tissue specimens were then collected from the do...
Burke MJ, Tomlinson JE, Blikslager AT, Johnson AL, Dallap-Schaer BL.Continuous digital cryotherapy experimentally prevents development and reduces severity of sepsis-associated laminitis. A sleeve style ice boot where ice is in direct contact with the skin, and water drains from the boot is being used clinically for distal limb cryotherapy. The degree of cooling achieved by this boot is unknown. Objective: Evaluate skin and lamellar cooling after application of the ice sleeve in healthy horses, and the same horses during an endotoxaemia model. Methods: Prospective study, crossover design. Methods: In eight healthy horses thermocouples were inserted into dorsal...
Magnusson CB, Poulsen KP, Budde JA, Hartmann FA, Aulik NA, Raabis SM, Moreira ASD, Darien BJ, Peek SF.Periodic lack of availability and high cost of commercially produced isotonic fluids for intravenous (IV) use in horses have increasingly led to use of home-made or commercially compound fluids by veterinarians. Data regarding the quality control and safety of compounded fluids would be of benefit to equine veterinarians. Objective: To compare electrolyte concentrations, sterility, and endotoxin contamination of commercially available fluids to 2 forms of compounded isotonic crystalloid fluids intended for IV use in horses. Methods: Prospective study. Two methods of preparing compounded crysta...
Bonelli F, Meucci V, Divers TJ, Wagner B, Intorre L, Sgorbini M.Endotoxemia represents a significant clinical and economic problem for the equine industry. This study assesses the kinetics of soluble CD14 (sCD14), chemokine (CC motif) ligand 2 (CCL2), interleukin 10 (IL-10) and plasma procalcitonin (PCT) in healthy horses after the intravenous infusion of lipopolysaccharide (LPS). The aim was to contribute to the basic understanding of the equine species-specific kinetics of these molecules in response to LPS exposure, which could support further findings in clinical studies and identify valuable inflammatory biomarkers for equine practice. Eleven healthy ...
Jones JL, Doherty TJ, Rohrbach BW.Total serum nitrate/nitrite concentration (SNN in µM L−1), an indirect measure of nitric oxide (NO), has been reported to be increased during critical illness in people and dogs. The relationship of NO to critical illness in horses is unknown. The purpose of this study was to quantify and compare SNN in normal, endotoxin treated, and horses with naturally acquired colic requiring surgical intervention.
Werners AH.Endotoxins, constituents of the cell wall of gram-positive and gram-negative bacteria, regularly result in severe illness and death in horses. In endotoxaemia, these constituents are present in the systemic circulation; in septicaemia, whole microbes invade normally sterile parts of the body. Interaction of these endotoxins with pathogen recognition receptors leads to an inflammatory response that cannot always be sufficiently contained and hence needs direct treatment. Over the last decennia, our understanding of the pathophysiology of endotoxaemia and septicaemia has significantly increased....
Fogle J, Jacob M, Blikslager A, Edwards A, Wagner B, Dean K, Fogle C.Clinically useful biomarkers are needed for early identification of endotoxaemic horses. Soluble CD14 (sCD14) is amplified early in response to inflammatory signals, including bacterial lipopolysaccharide (LPS), and may prove a useful biomarker for clinical endotoxaemia. Objective: The aim of this study was to determine if sCD14 could serve as a more reliable biomarker of the clinical signs of endotoxaemia, compared to measuring LPS alone. Methods: Prospective observational study in horses at a veterinary teaching hospital. Methods: Plasma samples were collected from 20 healthy horses and 35 h...
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...
Lilliehöök I, Tvedten HW, Bröjer J, Edner A, Nostell K.Neutrophil myeloperoxidase content is determined by the Advia 2120 hematology system by staining characteristics. Changes in myeloperoxidase staining are shown by location of neutrophils on Advia peroxidase dot plots and as myeloperoxidase index (MPXI). Significant changes in MPXI have been reported during severe inflammation in horses, dogs, and people but conclusions were inconsistent. Objective: Infusion of endotoxin was used to initiate an inflammatory stimulus under controlled conditions and over a longer time period than in previous studies to document kinetics of changes in neutrophil n...
Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G.Laminitis is one of the most common diseases in horses. It is not only painful for the animal, but also has a significant financial impact on the equine industry. This multifactorial disease affects the connective tissue of the hoof. However, the pathogenesis of laminitis is still not fully understood. Endotoxins, also known as lipopolysaccharides (LPS), and bacterial exotoxins seem to play an important role during the development of laminitis. The aim of our study was to investigate the effect of increasing LPS concentrations (0, 2.5, 5, 10, and 100 μg/mL) on cell viability of isolated epide...
Bauquier JR, Tudor E, Bailey SR.Despite the severity and common occurrence of equine endotoxaemia, the available anti-endotoxic treatments do not effectively target key inflammatory mechanisms such as leucocyte activation and cytokine production. In this study, four compounds with potential anti-endotoxic effects, namely rolipram, azithromycin, ethyl pyruvate and metformin, were investigated in vitro using equine whole blood stimulated with bacterial lipopolysaccharide. TNF-α and IL-1β production were measured in plasma. Rolipram was the most potent inhibitor of cytokine production (IC50 0.84 and 4.68 μm for TNF-α and IL...
Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G.The pathogenesis of laminitis is not completely identified and the role of endotoxins (lipopolysaccharides, LPS) in this process remains unclear. Phytogenic substances, like milk thistle (MT) and silymarin, are known for their anti-inflammatory and antioxidant properties and might therefore have the potential to counteract endotoxin induced effects on the hoof lamellar tissue. The aim of our study was to investigate the influence of endotoxins on lamellar tissue integrity and to test if MT and silymarin are capable of inhibiting LPS-induced effects in an in vitro/ex vivo model. In preliminary ...
Patan-Zugaj B, Gauff FC, Plendl J, Licka TF.To investigate effects of endotoxin on leukocyte activation and infiltration of the laminar tissue in isolated perfused equine limbs. Methods: 10 right forelimbs and 3 left forelimbs collected from 10 healthy adult horses after slaughter at a licensed abattoir. procedures: Isolated right forelimbs were randomly assigned to 2 groups (5 forelimbs/group): perfusion of the distal portion for 10 hours with 80 ng of endotoxin/L and perfusion under the same conditions without endotoxin. After perfusion, samples for immunohistochemical detection of leukocytes (by use of antibodies against calprotectin...
Watts AE, Ness SL, Divers TJ, Fubini SL, Frye AH, Stokol T, Cummings KJ, Brooks MB.To evaluate the effects of clopidogrel on clinical and clinicopathologic variables in healthy horses with experimentally induced endotoxemia. Methods: 12 adult mares. Procedures-Horses were assigned with a randomization procedure to receive clopidogrel (4 mg/kg, once, then 2 mg/kg, q 24 h; n = 6) or a placebo (6) through a nasogastric tube. After 72 hours of treatment, horses received lipopolysaccharide (LPS; 30 ng/kg, IV). Heart rate, respiratory rate, rectal temperature, CBC variables, plasma fibrinogen concentration, serum tumor necrosis factor-α concentration, plasma von Willebrand factor...
Moore JN, Vandenplas ML.Some veterinarians describe particularly sick horses or neonatal foals as being endotoxemic, whereas others refer to the same animals as having the systemic inflammatory response syndrome. This article reviews the basis for the use of each of these terms in equine practice, and highlights the mechanisms underlying the response of the horse's innate immune system to key structural components of the microorganisms that initiate these conditions, including how some of those responses differ from other species. Current approaches used to treat horses with these conditions are summarized, and cauti...
Wong DM, Sponseller BA, Alcott CJ, Agbedanu PN, Wang C, Hsu WH.To evaluate the effect of IV administration of polymyxin B on clinical and serum biochemical variables in foals with experimental endotoxemia. Methods: Prospective experimental study. Methods: 14 healthy neonatal foals. Methods: Foals were randomly assigned to a treatment or control group and were administered a single dose of lipopolysaccharide (0.5 μg/kg [0.23 μg/lb]) IV over 30 minutes. The treatment group received polymyxin B (6,000 U/kg [2,727 U/lb], IV) immediately after completion of lipopolysaccharide infusion; the control group was administered an equal volume of saline (0.9% NaCl) ...
Tadros EM, Frank N, De Witte FG, Boston RC.To test the hypothesis that glucose and insulin dynamics during endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). Methods: 6 healthy adult mares 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 insulin-modified frequently sampled IV glucose tolerance tests were performed 27 hours before and then repeated at 0.5 and 21 hours after infusion. Results were ass...
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...
Kwon S, Moore JN, Robertson TP, Hurley DJ, Wagner B, Vandenplas ML.Although clinical evidence of endotoxemia has been associated with the development of acute laminitis in hospitalized horses with gastrointestinal diseases and endotoxins have been detected in the circulation of horses with experimentally-induced laminitis, it is unclear what role, if any, endotoxins have play the pathogenesis of the disease. Therefore, in the present study we compared the effects of endotoxin infusion to that of intra-gastric administration of mixed carbohydrate (CHO) on clinical signs of laminitis, plasma concentrations of TNF-α and IL-10, and laminar tissue expression of 2...
Scior T, Alexander C, Zaehringer U.There is literature evidence gathered throughout the last two decades reflecting unexpected species differences concerning the immune response to lipid IVa which provides the opportunity to gain more detailed insight by the molecular modeling approach described in this study. Lipid IVa is a tetra-acylated precursor of lipid A in the biosynthesis of lipopolysaccharide (LPS) in Gram-negative bacteria. Lipid A of the prototypic E. coli-type is a hexa-acylated structure that acts as an agonist in all tested mammalian species by innate immunorecognition via the Toll-like receptor 4 (TLR4)/myeloid d...
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...
Fossum C, Hjertner B, Olofsson KM, Lindberg R, Ahooghalandari P, Camargo MM, Bröjer J, Edner A, Nostell K.The expression of tlr4, md2 and cd14 was studied in equine blood leukocytes and in intestinal samples using real time PCR. The stability of three commonly used reference genes, glyceraldehyde-3P-dehydrogenase (GAPDH), hypoxantine ribosyltransferase (HPRT) and succinate dehydrogenase complex subunit A (SDHA), was evaluated using qbase(PLUS). The equine peripheral blood mononuclear cells (eqPBMC) examined were either stimulated in vitro with Phorbol 12-myristate 13-acetate (PMA) and ionomycin or with the CpG oligodeoxynuclotide 2216 (CpG-ODN 2216) or obtained from horses before, during and after...
Tadros EM, Frank N, Newkirk KM, Donnell RL, Horohov DW.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...
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...
Patan-Zugaj B, Gauff FC, Licka TF.To examine the effect of endotoxins on metabolism and histopathologic changes of isolated perfused equine forelimbs. Methods: Forelimbs (comprising the metacarpus and digit) were collected from cadavers of 12 healthy adult horses after slaughter at an abattoir (14 limbs; 1 forelimb of 10 horses and both forelimbs of 2 horses). Methods: Forelimbs were perfused for 10 hours with autologous blood, with and without the addition of endotoxin (80 ng of lipopolysaccharide [LPS]/L). Two limbs of the endotoxin exposure group and 2 nonperfused limbs were loaded to failure of the suspensory apparatus of ...
Tadros EM, Frank N.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...
Aharonson-Raz K, Lohmann KL, Townsend HG, Marques F, Singh B.Heaves, an obstructive neutrophilic airway inflammation of horses, is triggered by dust components such as endotoxin and has similarities to human asthma. Pulmonary intravascular macrophages (PIMs) increase horses' sensitivity to endotoxin-induced lung inflammation; however, their role in an airborne pathology remains unknown. Therefore, we investigated the role of PIMs in the development of heaves in horses. Clinical and inflammatory responses were evaluated following induction of heaves by moldy hay exposure and PIM depletion with gadolinium chloride (GC). Mares (N = 9) were exposed to four ...
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...
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...
Pirie RS, Dixon PM, McGorum BC.Mould extract inhalation challenges have been used extensively in the investigation of heaves. Such challenges have induced pulmonary neutrophilic inflammation and dysfunction, consistent with, but less severe than the natural disease. However, the method of mould extract production is likely to result in endotoxin contamination. Objective: To investigate whether insufficient dose delivery was responsible for the shortfall in response to inhaled extract compared with natural disease, and whether endotoxin contamination of mould extract contributed to the pulmonary inflammation and dysfunction....
Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G.The pathogenesis of laminitis is not completely identified and the role of endotoxins (lipopolysaccharides, LPS) in this process remains unclear. Phytogenic substances, like milk thistle (MT) and silymarin, are known for their anti-inflammatory and antioxidant properties and might therefore have the potential to counteract endotoxin induced effects on the hoof lamellar tissue. The aim of our study was to investigate the influence of endotoxins on lamellar tissue integrity and to test if MT and silymarin are capable of inhibiting LPS-induced effects in an in vitro/ex vivo model. In preliminary ...
Tóth F, Frank N, Elliott SB, Geor RJ, Boston RC.To evaluate the effects of endotoxin administered IV on glucose and insulin dynamics in horses. Methods: 16 healthy adult mares. Methods: Each week of a 2-week randomized crossover study, each horse received an IV injection (duration, 30 minutes) of Escherichia coli O55:B5 lipopolysaccharide (LPS) in 60 mL of sterile saline (0.9% NaCl) solution (20 ng/kg) or sterile saline solution alone (control treatment). Frequently sampled IV glucose tolerance test procedures were performed at 24 hours before (baseline) and 24 and 48 hours after injection; glucose and insulin dynamics were assessed via min...
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...
Parsons CS, Orsini JA, Krafty R, Capewell L, Boston R.To identify risk factors for development of acute laminitis in horses during hospitalization for illness or injury. Methods: Retrospective case-control study. Methods: 73 horses that developed laminitis (case horses) and 146 horses that did not develop laminitis (control horses) during hospitalization. Methods: Case and control horses were matched in a 2:1 ratio by the date on which each horse was evaluated. Potential risk factors investigated included age, breed, and sex; highest and lowest values recorded during hospitalization for fibrinogen concentration, WBC count, PCV, and total solids c...
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...
Fessler JF, Bottoms GD, Coppoc GL, Gimarc S, Latshaw HS, Noble JK.Endotoxin (LPS) was quantitated in experimental subjects and in horses with naturally occurring gastrointestinal strangulation obstruction and/or septicaemic diseases to establish the fate of LPS and the clinical usefulness of the Limulus amoebocyte lysate (LAL) assay. The assay was validated for sensitivity (10 pg/ml), recovery (90 to 106 per cent), intra-assay precision (CV = 5.5 per cent) inter-assay precision (CV = 11 per cent), and stability of diluted, heat treated, frozen samples (at least 90 days). Plasma concentrations of LPS after sublethal (3 micrograms/kg) jugular or portal vein bo...
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...
Oliveira-Filho JP, Badial PR, Cunha PH, Peiró JR, Araújo JP, Divers TJ, Winand NJ, Borges AS.Hepcidin has been found to be the key regulator of iron metabolism that leads to hypoferremia during inflammation. Recent work has shown that equine hepcidin is predominantly expressed in the liver of horses. In this study, hepcidin gene expression was determined in the liver and bone marrow of six healthy horses after iv infusion of Escherichia coli O55:B5 LPS. The IL-6 gene expression was also determined in liver and bone marrow samples. Clinical and laboratory evaluations were measured at multiple time points between 0 and 240 h post-LPS infusion (PI). Liver and bone marrow biopsies were ...
Sykes BW, Furr MO.The pathophysiology of endotoxaemia, a leading cause of death in the horse, is beginning to be understood in greater detail. Endotoxin may be absorbed into the systemic circulation in a number of different ways: most commonly the body's normal defense mechanisms are disrupted or bypassed, or the normal clearance mechanisms overwhelmed. Following this wide-spread effects are observed, although the most significant are seen in the cardiovascular system. Fever, arterial hypoxaemia and signs of abdominal pain are also common. With increased understanding of the disease new therapeutic agents have ...
King JN, Gerring EL.Post operative ileus (POI) is a common and serious complication of colic surgery in the horse. There is a high correlation between the incidence of POI and the presence of ischaemic bowel, suggesting a role for endotoxin. 0.1 micrograms/kg endotoxin was administered intravenously to six ponies with chronically implanted gastrointestinal electromechanical recording devices. It produced profound disruption of normal fasting bowel motility patterns, with an inhibition of gastric contraction amplitude and rate, left dorsal colon contraction product and small colon spike rate. In the small intestin...
Tóth F, Frank N, Chameroy KA, Bostont RC.Insulin resistance (IR) is a risk factor for pasture-associated laminitis in equids and alimentary carbohydrate overload may trigger laminitis. Whether glucose metabolism responses to carbohydrate overload are more pronounced in insulin-resistant horses requires further study. Objective: Horses pretreated with endotoxin to alter insulin sensitivity differ significantly in their glucose and insulin responses to carbohydrate overload. Methods: Horses (n=24) were divided into 3 groups. A lipopolysaccharide (LPS; n=8) group that received endotoxin as an 8 h 7.5 ng/kg bwt/h i.v. continuous rate inf...
Sprouse RF, Garner HE, Green EM.Thirteen (65 per cent) of 20 horses subjected to carbohydrate overload developed Obel Grade 3 lameness within 56 h. Increases in plasma endotoxin from control levels of less than 0.1 ng/litre to values ranging from 2.4 to 81.53 ng/litre were measured in 11 (85 per cent) of 13 horses during the onset of Obel Grade 3 lameness. Obel Grade 3 lameness was associated with rises in plasma Gram-negative endotoxin levels in 11 (92 per cent) of 12 horses. Two peak increases separated by 16 h were verified in five (45 per cent) of 11 horses that exhibited both endotoxaemia and Obel Grade 3 lameness. The ...
Henry MM, Moore JN.Increasing evidence has demonstrated the importance of monocyte procoagulant activity (PCA) in the pathogenesis of coagulopathies in a variety of diseases. Because endotoxin precipitated coagulopathies are common sequelae to intestinal ischemia/endotoxemia in the equine species, we investigated the ability of equine peripheral blood monocytes to express PCA. Monocytes isolated from five healthy adult horses were incubated in vitro with Escherichia coli endotoxin (10 micrograms), and the PCA was measured by the ability of cellular lysates to accelerate the clotting times of equine plasma in a m...
Barton MH, Morris DD, Norton N, Prasse KW.Thirteen coagulation tests evaluating hemostatic and fibrinolytic indices and serum cytokine and plasma endotoxin concentrations were obtained in 34 foals with a positive sepsis score (septic group) and 46 age-matched healthy foals. Compared to healthy foals, the prothrombin, activated partial thromboplastin, and whole blood recalcification times were significantly longer in septic foals. The fibrinogen and fibrin degradation products concentrations, percent plasminogen, alpha-2 antiplasmin, and plasminogen activator inhibitor activities, and tumor necrosis factor and interleukin-6 activities ...
Wilson RC, Moore JN, Eakle N.The pharmacokinetics of gentamicin (3 mg/kg of body weight) were evaluated in 6 healthy horses and in 6 horses after they were given Escherichia coli endotoxin (0.113 microgram/kg). In the horses given endotoxin, there were a maximum temperature increase of 1.97 +/- 0.44 degrees (C) and a fever index (between the 2 groups) of 8.754 units. Other mild signs of endotoxemia also occurred. Statistically significant changes were not observed in the rate constants for distribution (alpha) or elimination (beta) or in body clearance (ClB) of gentamicin in the 2 groups of horses. In the horses given end...
Werners AH, Bryant CE.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.
Figueiredo MD, Moore JN, Vandenplas ML, Sun WC, Murray TF.To evaluate proinflammatory effects of the second-generation synthetic lipid A analogue E5564 on equine whole blood and isolated monocytes and to determine the ability of E5564 to prevent LPS (lipopolysaccharide)-induced procoagulant activity (PCA); tumor necrosis factor (TNF)-alpha production; and mRNA expression of TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-10 by equine monocytes. Methods: Venous blood samples obtained from 19 healthy horses. Methods: Whole blood and monocytes were incubated with Escherichia coli O111:B4 LPS, E5564, or E5564 plus E coli O111:B4 LPS. Whole blood and cell...
Lilliehöök I, Tvedten HW, Bröjer J, Edner A, Nostell K.Neutrophil myeloperoxidase content is determined by the Advia 2120 hematology system by staining characteristics. Changes in myeloperoxidase staining are shown by location of neutrophils on Advia peroxidase dot plots and as myeloperoxidase index (MPXI). Significant changes in MPXI have been reported during severe inflammation in horses, dogs, and people but conclusions were inconsistent. Objective: Infusion of endotoxin was used to initiate an inflammatory stimulus under controlled conditions and over a longer time period than in previous studies to document kinetics of changes in neutrophil n...
Moore JN, Barton MH.Although recognition of clinical signs of endotoxemia is not difficult, determining the underlying cause for the development of endotoxemia may be a challenging task. For this reason, importance must be placed on performance of a thorough physical examination, attention to detail, and determination of whether or not surgical intervention is required. In most instances, a definitive diagnosis may require repeated examinations and laboratory work. In the meantime, affected animals require treatment for endotoxemia, with the aim being to reduce the duration of endotoxemia, prevent the interaction...
Fogle J, Jacob M, Blikslager A, Edwards A, Wagner B, Dean K, Fogle C.Clinically useful biomarkers are needed for early identification of endotoxaemic horses. Soluble CD14 (sCD14) is amplified early in response to inflammatory signals, including bacterial lipopolysaccharide (LPS), and may prove a useful biomarker for clinical endotoxaemia. Objective: The aim of this study was to determine if sCD14 could serve as a more reliable biomarker of the clinical signs of endotoxaemia, compared to measuring LPS alone. Methods: Prospective observational study in horses at a veterinary teaching hospital. Methods: Plasma samples were collected from 20 healthy horses and 35 h...
Berndt A, Derksen FJ, Edward Robinson N.Inflammatory airway disease is common in stabled horses, with a prevalence of 17.3% in Michigan pleasure horses. Stable dust is rich in endotoxin, which may induce neutrophilic airway inflammation. Climatological conditions (ambient temperature and relative humidity) may influence endotoxin concentrations in pastures. The aim of this project was to determine if endotoxin levels in the breathing zone of horses in stables were higher than of horses on pasture, and if the endotoxin on pasture was associated with climatological conditions. Endotoxin exposure of six horses that were stabled or on p...
Durando MM, MacKay RJ, Linda S, Skelley LA.Polymyxin B and an antiserum against an Re mutant Salmonella typhimurium were evaluated for protective effect in an equine model endotoxemia. Six 3- to 5-month-old foals were given endotoxin (0.25 micrograms/kg of body weight) IV after no pretreatment, or pretreatment with polymyxin B (6,000 U/kg, IV) or S typhimurium antiserum (1.5 ml/kg, IV). When given without pretreatment, endotoxin caused transient recumbency and increases in rectal temperature, and heart and respiratory rates. In addition, leukopenia and increases in circulating tumor necrosis factor (TNF) and interleukin 6 (IL-6) activi...
Morresey PR, Mackay RJ.To measure serum polymyxin B concentration after single and repeated IV infusions in horses. Methods: 5 healthy horses. Methods: In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion a...
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...
Patan-Zugaj B, Gauff FC, Licka TF.To examine the effect of endotoxins on metabolism and histopathologic changes of isolated perfused equine forelimbs. Methods: Forelimbs (comprising the metacarpus and digit) were collected from cadavers of 12 healthy adult horses after slaughter at an abattoir (14 limbs; 1 forelimb of 10 horses and both forelimbs of 2 horses). Methods: Forelimbs were perfused for 10 hours with autologous blood, with and without the addition of endotoxin (80 ng of lipopolysaccharide [LPS]/L). Two limbs of the endotoxin exposure group and 2 nonperfused limbs were loaded to failure of the suspensory apparatus of ...
Hart KA, Barton MH, Vandenplas ML, Hurley DJ.Low-dose hydrocortisone (LDHC) therapy modulates inflammatory responses in adults and improves outcomes in some septic adults and neonates, but its immunologic effects have not been evaluated in neonates. The objective of this study was to evaluate effects of LDHC therapy on ex vivo immune function in neonatal horses (foals). We hypothesized that LDHC treatment would dampen proinflammatory responses without impairing neutrophil function. Hydrocortisone (1.3 mg/kg/d i.v.) was administered to foals in a tapering 3.5 d course. Peripheral blood leukocytes were collected from foals before, during, ...
