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.
Zahradnik E, Sander I, Lotz A, Liebers V, Thullner I, Tacke S, Raulf M.The study aimed to determine the allergen, endotoxin and β-(1,3)-glucan concentrations at various areas on a university campus of veterinary medicine. Methods: Dust samples were collected four times a year for three years using electrostatic dust collectors (EDC) at 25 different locations on a campus of veterinary medicine and in laboratories of inorganic chemistry as a control area representing animal-free environment. Major animal allergens from dog, cat, horse, cattle and mouse, domestic mite (DM) allergens, and β-(1,3)-glucan were measured using enzyme immunoassays and endotoxin using th...
Mercer MA, Davis JL, McKenzie HC, Messenger KM, Schaefer E, Council-Troche RM, Werre SR.Acetaminophen has been evaluated in horses for treatment of musculoskeletal pain but not as an antipyretic. Objective: To determine the pharmacokinetics and efficacy of acetaminophen compared to placebo and flunixin meglumine in adult horses with experimentally induced endotoxemia. Methods: Eight university owned research horses with experimentally induced endotoxemia. Methods: Randomized placebo controlled crossover study. Horses were treated with acetaminophen (30 mg/kg PO; APAP), flunixin meglumine (1.1 mg/kg, PO; FLU), and placebo (PO; PLAC) 2 hours after administration of LPS. Plasma ...
Townsend M, Fowler B, Aulakh GK, Singh B.Endotoxin-induced diseases cause significant mortality and morbidity in the horse, leading to enormous economic damage to the equine industry. Neutrophils play a critical role in initiating the immune response in the lung. Pattern recognition receptors (PRRs) are programmed to recognize microbial structures unique to pathogens and mount an immune response. Pentraxin 3 (PTX3) is a PRR that is produced at sites of inflammation by many cell types upon stimulation by pro-inflammatory cytokines and agonists, such as endotoxins [also known as lipopolysaccharides (LPS)]. Pentraxin 3 recognizes and bi...
Faber E, Tshilwane SI, Van Kleef M, Pretorius A.Transcriptome analysis was used to characterise the in vitro primary and secondary immune responses induced in horse peripheral blood mononuclear cells (PBMC) stimulated for 24 h with the individual recombinant proteins of a virulent AHSV serotype 4 (AHSV4) field isolate (rAHSV4 proteins) that were previously expressed in Escherichia coli (E. coli). The results showed that the E. coli contamination products greatly affected the innate and humoral immune response transcripts. Hence, the impact of E. coli contamination products present in the individual rAHSV4 proteins on the translational immu...
Gomez DE, Leclere M, Arroyo LG, Li L, John E, Afonso T, Payette F, Darby S.This study describes the clinicopathological findings, diagnostic approach, treatment, and factors associated with non-survival of diarrheic horses admitted to 4 Canadian university teaching hospitals between 2015 and 2019. A total of 300 horses, ≥1-year-old, with acute diarrhea were included and represented 1.6% (300/18 481; range: 0.7 to 3%) of admissions during that period, 70% of the horses survived to discharge. Testing for enteropathogens was limited to a single fecal culture for Salmonella spp. in most cases. An enteropathogen was identified in 14% (42/300) of the horses, but in the h...
Kimura S, McCoy AM, Boothe DM, Wooldridge AA, Graff E, Hammack SM, Cresci L, Hofmeister E, Lascola KM.To describe misoprostol pharmacokinetics and anti-inflammatory efficacy when administered orally or per rectum in endotoxin-challenged horses. Methods: 6 healthy geldings. Methods: A randomized 3-treatment crossover design was performed with a minimum washout period of 28 days between treatment arms. Prior to endotoxin challenge (lipopolysaccharide, 30 ng/kg IV over 30 minutes), horses received misoprostol (5 µg/kg once) per os (M-PO) or per rectum (M-PR) or water as control (CON). Clinical parameters were evaluated and blood samples obtained to measure plasma misoprostol free acid concentrat...
Page AE, Wood C, Partridge E, Horohov DW, Adam E.The use of lipopolysaccharide to induce a localized source of inflammation (acute synovitis) and allow for monitoring of changes in systemic mRNA expression has been recently reported. Here, the goal was to maintain a significant systemic mRNA response while limiting the severity of lameness such that this model can be used to examine the effects of various anti-inflammatory treatment modalities on mRNA expression. Three mixed breeds, four-year-old geldings were utilized for this study. One milliliter of phosphate-buffered saline containing 1,000 ng or less of lipopolysaccharide from E. coli O...
Hector RC, Rezende ML, Nelson BB, Monnet E.Endotoxaemia causes untoward inflammatory-mediated effects that might be attenuated by dexmedetomidine. Objective: To evaluate the effects of a dexmedetomidine intravenous (IV) infusion on systemic and intestinal haemodynamics and arterial blood gas values in sevoflurane-anaesthetised horses administered Escherichia coli O55:B5 lipopolysaccharides (LPS). Methods: Randomised controlled in vivo experiment. Methods: A total of 13 horses weighing 456 ± 86 kg (mean ± standard deviation) and aged 13.9 ± 9.0 years donated for euthanasia underwent ventral midline celiotomy using sevoflurane...
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...
Scavone D, Sgorbini M, Borges AS, Oliveira-Filho JP, Vitale V, Paltrinieri S.Paraoxonase-1 (PON-1) is an antioxidant enzyme, whose activity decreases during the acute phase response in many species. Little is known about PON-1 and its role as a negative acute phase protein during septic inflammation in horses, but promising findings about its utility in diagnosing SIRS and predicting the outcome in diseased horses, were recently highlighted. The objective of the study was to investigate the behaviour of PON-1 in horses after experimentally induced endotoxemia. To this aim, PON-1 activity was measured on 66 plasma samples collected from six clinically healthy mares, pre...
Kilcoyne I, Nieto JE, Watson JL, Galuppo LD, Borjesson DL.Endotoxemia is a leading cause of morbidity and mortality in the equine industry, with colic being the most common cause of endotoxemia in horses. The objective of this study was to evaluate the safety and potential efficacy of a single dose of allogeneic equine bone marrow derived mesenchymal stem cells (BM-MSCs) in horses after the IV administration of lipopolysaccharide (LPS). Six horses were administered an IV infusion of 30 ng/kg LPS (O55:B5 Escherichia coli) in 500 ml saline over 30 min. Immediately after infusion test horses (n = 3) were administered 100 × 10 allogeneic BM-MSCs diluted...
Anderson MJ, Ibrahim AS, Cooper BR, Woolcock AD, Moore GE, Taylor SD.Sepsis is associated with ascorbic acid (AA) depletion and critical illness-related corticosteroid insufficiency (CIRCI) in humans. Objective: Intravenous infusion of lipopolysaccharide (LPS) would (a) decrease endogneous AA concentrations, (b) induce CIRCI and (c) administration of a combination of AA and hydrocortisone (HC) would have decreased indices of inflammation compared to either drug alone. Methods: Thirty-two healthy horses. Methods: Randomized placebo-controlled experimental trial. Horses were assigned to 1 of 4 groups (saline, AA and HC, AA only, or HC only). Treatments were admin...
Perez-Ecija A, Buzon-Cuevas A, Aguilera-Aguilera R, Gonzalez-De Cara CA, Mendoza FJ.Preanalytical factors such as storage time and temperature are proved to induce marked artifactual changes in hematological parameters in horses, small animals and humans. These errors can mirror findings typical of endotoxemia, leading to dangerous misdiagnosis. Since donkeys are common in warm climates and remote regions, blood samples from this species can be subjected to long lasting travels from the farm to the nearest laboratory, frequently under suboptimal conditions. Moreover, as other equids, donkeys are prone to suffer endotoxemia. Nonetheless, stability has not been evaluated in sam...
Lilliehöök I, Bröjer J, Nostell K, Kindahl H, Tvedten HW, Edner A, Hagman R.Endotoxemia is a common and severe disease of horses. Most previous studies have monitored changes caused by a bolus dose of endotoxin over short time periods. Objective: We aimed to describe inflammatory responses to endotoxin with inflammatory and hematologic markers monitored over a longer time than has been performed in the past using more prolonged endotoxin exposures. Methods: Escherichia coli O55:B5 endotoxin was administered as a 6-hour continuous intravenous infusion of lipopolysaccharide (LPS) to eight horses. Blood cell counts, and prostaglandin F -metabolite (PGM), serum amyloid 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...
Blaue D, Schedlbauer C, Starzonek J, Gittel C, Brehm W, Blüher M, Pfeffer M, Vervuert I.Human obesity is linked with systemic inflammation. However, it is still controversial if equines produce more inflammatory cytokines with increasing body weight and if the production of those show breed type specific patterns. The main objective of this study was to determine if diet induced obesity is associated with increased inflammatory signatures in adipose tissue of equines and if a breed predisposition exists between ponies and horses. Additionally, we aimed to identify adipose tissue depot differences in inflammatory cytokine expression. Nineteen healthy, non-overweight and metabolica...
Dória RGS, Freitas SH, Laskoski LM, Arruda LP, Shimano AC.Surgical site infection of abdominal incisions is an important complication after laparotomy with increased risk of incisional hernia formation in horses. This study aims to evaluate the healing process of abdominal incisions and correlate peritonitis with the occurrence of surgical site infection and incisional hernias. Nine horses underwent standardized laparotomy, intestinal exploration, and induced septic peritonitis. Standardized relaparotomy was performed two (n = 3), four (n = 3), and six (n = 3) months later to evaluate the abdominal cavity for adhesions and to collect the sutured v...
Patan-Zugaj B, Egerbacher M, Licka TF.Angiogenesis and sepsis-related equine laminitis have several features in common. Both events can be induced by endotoxin (lipopolysaccharide- LPS) and both are associated with increased expression of the enzyme cyclooxygenase (COX), of which two isoforms (COX-1 and COX-2) exist. To examine the causal relationship between LPS exposure and COX expression and to investigate the tissue distribution of COX in the LPS-exposed tissue, the technique of extracorporeal haemoperfusion of isolated equine forelimbs was utilized. Perfusion was performed for 10 hr under physiological conditions (control-pe...
Hwang J, Golla V, Metwali N, Thorne PS.Adverse respiratory health effects in the agricultural industry have been linked to particulate endotoxin exposure. However, whether the endotoxin concentration is significantly correlated to the size of the particle remains an open question. To date, limited research has been conducted to assess particulate endotoxin exposures in the agricultural industry in general or the equine industry in particular. A task-based exposure assessment was conducted to characterize the endotoxin levels of inhalable and respirable particles on four Kentucky farms during the summer season. We conducted personal...
Cacciolatti C, Meyer-Ficca ML, Southwood LL, Meyer RG, Bertolotti L, Zarucco L.To evaluate effects of poly(ADP-ribose) polymerase-1 (PARP1) inhibitors on the production of tumor necrosis factor-α (TNF-α) by interferon-γ (IFN-γ)- and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) of horses as an in vitro model of inflammation in horses. Methods: 1,440 samples of PBMCs from 6 healthy research horses. Methods: From heparinized whole blood samples, PBMC cultures were obtained. An initial dose-response trial on 48 PBMC samples from 2 horses (24 samples each) was used to determine concentrations of IFN-γ and LPS for use as low- and high-lev...
Hay AN, Potter A, Kasmark L, Zhu J, Leeth CM.Varying susceptibility exists among mammalian species to the development of potentially fatal endotoxemia due to gram-negative bacteria molecular component, lipopolysaccharide (LPS). Toll-like receptor 4 (TLR4) is responsible for LPS-associated immune response and is expressed on numerous immune cells including B lymphocytes. TLR4 is expressed in a functional form on mouse B lymphocytes, a species much less susceptible to endotoxemia compared with humans who are highly sensitive to endotoxin. Humans possess B lymphocytes that are not responsive to LPS. Likewise, horses are highly susceptible t...
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....
Pirie RS, Collie DD, Dixon PM, McGorum BC.Equine heaves is a naturally occurring organic dust-induced asthma characterized by airway neutrophilia, mucus hypersecretion and obstructive lung dysfunction. However, the relative role of different dust components in disease severity remains unclear. Objective: This study investigated the relative contribution of inhaled endotoxin and organic dust particulates (mainly mould spores) in inducing heaves in heaves-susceptible horses. Methods: Control and heaves-susceptible horses received inhalation challenges with hay dust suspension (HDS) before and after lipopolysaccharide (LPS) depletion. He...
Neuder LE, Keener JM, Eckert RE, Trujillo JC, Jones SL.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...
Samadi S, Wouters IM, Houben R, Jamshidifard AR, Van Eerdenburg F, Heederik DJ.Workers in horse stables are likely exposed to high levels of organic dust. Organic dusts play a role in increased risk of inflammatory reactions and are associated with respiratory diseases. The aim of this study was to investigate dust, endotoxin, beta(1-->3)-glucan, and culturable microorganisms exposure levels in horse stables. Methods: Ambient (n = 38) and personal (n = 42) inhalable dust samples were collected using PAS-6 sampling heads. As a special measurement, we included sampling near the horses' heads. Samples were analyzed for endotoxin and beta(1-->3)-glucan by Limulus amebo...
Palmer JL, Bertone AL.The use of extremely small dosages of intra-articular E. coli lipopolysaccharide (LPS) endotoxin can create a model of synovitis that mimics acute synovitis in horses. Dosages of 5000 ng, 25 ng, 0.5 ng, 0.25 ng, 0.17 ng and 0.125 ng per joint were injected into various joints of a total of 6 horses. The dose response of LPS on clinical signs and synovial fluid parameters was evaluated at baseline and 12, 24, 36 and 48 h after LPS injection. Peripheral venous blood analysis was performed at baseline and at 0, 4, and 12 h after LPS injection. Dosages greater than 0.5 ng/joint resulted in clinica...
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...
Morris DD.Endotoxemia remains the leading cause of death in horses, being intimately involved in the pathogenesis of gastrointestinal disorders that cause colic and neonatal foal septicemia. Endotoxins, normally present within the bowel, gain access to the blood across damaged intestinal mucosa, or endotoxemia occurs when gram negative organisms proliferate in tissues. Endotoxins are removed from the circulation by the mononuclear phagocyte system, and the response of mononuclear phagocytes to these lipopolysaccharides (LPS) play an important role in determining the severity of clinical disease. Macroph...
Riihimäki M, Raine A, Elfman L, Pringle J.Airborne factors in a conventionally managed racing stable and markers of pulmonary inflammation in the stabled horses were investigated on 3 occasions at 6-month intervals, including 2 winter periods and the intervening summer period. The stable measurements included inside and outside ambient temperature and relative humidity, levels of total and respirable dust, endotoxin, and 1,3-beta-glucan. Horses (n = 12) were examined in detail clinically as well as by endoscopy, bronchoalveolar lavage (BAL) cytology, and real-time polymerase chain reaction (RT-PCR) analysis of BAL-cells for IL-6 and I...
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...
Toribio RE, Kohn CW, Hardy J, Rosol TJ.Hypocalcemia and hypomagnesemia are common in horses with sepsis and endotoxemia. We hypothesize that endotoxemia triggers a systemic inflammatory response that results in hypocalcemia and hypomagnesemia. The goal of this study was to determine the effect of endotoxin (lipopolysaccharide [LPS]) administration to healthy horses on serum parathyroid hormone (PTH), ionized calcium (Ca2+) and total calcium (tCa), ionized magnesium (Mg2+) and total magnesium (tMg), phosphate (Pi), potassium (K+), sodium (Na+), chloride (Cl-), and insulin concentrations, and on the urinary excretion of these electro...
Donovan DC, Jackson CA, Colahan PT, Norton N, Hurley DJ.Using an established standardized exercise test on a high-speed treadmill, thirteen Thoroughbred racehorses were exercised to fatigue (failure); blood samples were obtained before exercise, at failure, and at 2, 6, 24, 48, and 72 h after exercise. The exercise test induced a systemic inflammatory response characterized by a mild transient endotoxemia, leukocytosis, increased leukocyte expression of mRNA for tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, and IL-6, and increased circulating concentrations of TNF-alpha and prostaglandin F2 alpha (PGF 2 alpha), with the most pronounced change...
Pirie RS, Dixon PM, Collie DD, McGorum BC.To investigate whether inhaled endotoxin contributes to airway inflammation and dysfunction in stabled horses, control (n = 6) and asymptomatic heaves (previously termed chronic obstructive pulmonary disease)-susceptible (n = 7) horses were given inhalation challenges with 20, 200 and 2,000 microg of soluble Salmonella typhimurium Ra60 lipopolysaccharide (LPS). LPS inhalation induced a dose-dependent neutrophilic airway inflammatory response in both groups. Inhalation with 2,000 microg of LPS also induced detectable lung dysfunction in the heaves group. LPS inhalation did not alter clinical sc...
Nieto JE, MacDonald MH, Braim AE, Aleman M.Horses are exquisitely sensitive to bacterial endotoxin and endotoxaemia is common in colic cases. In this study, gene expression of inflammatory cytokines was characterised in the blood of healthy horses following i.v. administration of lipopolysaccharide (LPS). Six horses received an LPS infusion and 6 controls received an equivalent volume of saline. Gene expression of genes encoding interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, and tumour necrosis factor-alpha (TNF-alpha) was quantified by real-time PCR. Gene expression of all inflammatory cytokines was upregulated following administratio...
Thorne PS, Perry SS, Saito R, O'Shaughnessy PT, Mehaffy J, Metwali N, Keefe T, Donham KJ, Reynolds SJ.As a potent inflammatory agent, endotoxin is a key analyte of interest for studies of lung ailments in domestic environments and occupational settings with organic dust. A relatively unexplored advance in endotoxin exposure assessment is the use of recombinant factor C (rFC) from the Limulus pathway in a fluorometric assay. In this study, we compared airborne endotoxin concentrations in laboratory- and field-collected parallel air samples using the kinetic Limulus amebocyte lysate (LAL) assay and the rFC assay. Air sampling was performed using paired Institute of Occupational Medicine (IOM) sa...
Bailey SR, Adair HS, Reinemeyer CR, Morgan SJ, Brooks AC, Longhofer SL, Elliott J.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...
McGorum BC, Ellison J, Cullen RT.The concentrations of total and respirable airborne endotoxin in the breathing zone of a pony in 3 different management systems, on 8 occasions, are reported. Airborne endotoxin concentrations in all 3 systems were lower than those reported for many other agricultural environments. However, total airborne endotoxin concentrations in many of the conventional stables exceeded those which can induce pulmonary inflammation and bronchial hyper-responsiveness in normal human subjects, and exceeded those which can induce bronchoconstriction in humans with pre-existing pulmonary inflammation. Therefor...
Senior JM, Proudman CJ, Leuwer M, Carter SD.Endotoxaemia is frequently presumed on the basis of clinical signs in horses with colic. Objective: Measurements of plasma endotoxin (LPS) are rarely made in clinical cases and there is little information on the correlations between this variable, clinical variables and outcomes. Objective: To measure LPS levels in plasma of horses presented to the Philip Leverhulme Equine Hospital on admission and daily for up to 4 days and to relate LPS levels to selected clinical parameters, such as heart rate and packed cell volume, and outcomes. Methods: Blood samples were collected and stored at -20°C p...
Weese JS, Cote NM, deGannes RV.Clostridial colitis and endotoxaemia of intestinal origin are significant causes of morbidity and mortality in horses. Intestinal adsorbents are available for treatment of these conditions; however, little information exists supporting their use. Objective: To evaluate the ability of di-tri-octahedral smectite to bind to Clostridium difficile toxins A and B, C. perfringens enterotoxin and endotoxin, inhibit clostridial growth and the actions of metronidazole in vitro. Methods: Clostridium difficile toxins, C. perfringens enterotoxin and endotoxin were mixed with serial dilutions of di-tri-octa...
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...
Cook VL, Jones Shults J, McDowell M, Campbell NB, Davis JL, Blikslager AT.Absorption of endotoxin across ischaemic-injured mucosa is a major cause of mortality after colic surgery. Recent studies have shown that flunixin meglumine retards mucosal repair. Systemic lidocaine has been used to treat post operative ileus, but it also has novel anti-inflammatory effects that could improve mucosal recovery after ischaemic injury. Objective: Systemic lidocaine ameliorates the deleterious negative effects of flunixin meglumine on recovery of mucosal barrier function. Methods: Horses were treated i.v. immediately before anaesthesia with either 0.9% saline 1 ml/50 kg bwt, flun...
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...
Peek SF, Semrad S, McGuirk SM, Riseberg A, Slack JA, Marques F, Coombs D, Lien L, Keuler N, Darien BJ.This prospective study compared survival rates of critically ill and septic foals receiving 1 of 2 different types of commercial equine plasma and analyzed admission variables as possible predictors of survival. Standardized clinical, hematologic, biochemical, and hemostatic admission data were collected and foals received either conventional commercially available hyperimmune equine plasma or equine plasma specifically rich in antiendotoxin antibodies in a double-blinded, coded fashion. Sepsis was defined as true bacteremia or sepsis score >11. Overall survival rate to discharge was 72% (4...
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...
King JN, Gerring EL.The Limulus amoebocyte lysate assay was used to test for the presence of endotoxin in 37 clinical cases of equine colic. Positive plasma titres were detected in 10 cases and the presence of endotoxin was significantly correlated with a high heart rate, a high packed cell volume and a poor prognosis. High levels of endotoxin were detected in gut contents taken from several sites in the gastrointestinal tract of normal horses.
Kelmer G.Endotoxemia is a major cause of morbidity and mortality in horses affected by colic. This article briefly reviews the pathogenesis of endotoxemia in horses with colic, reviews current established treatments, and describes new advances in the treatment of endotoxemia.
Singh Suri S, Janardhan KS, Parbhakar O, Caldwell S, Appleyard G, Singh B.Toll-like receptor (TLR) is a key component in launching innate immune response to microbial challenge. TLR4 and TLR2 are recognized as specific receptors for components of Gram-negative and Gram-positive bacteria, respectively. Horses are extremely sensitive to endotoxin-induced cardiopulmonary distress and mortality which causes significant economic losses. To date, there are no data on the expression of TLR4 and TLR2 in horse lungs. Therefore, we examined the expression of TLR4 and TLR2 in lungs from normal or Escherichia coli lipopolysaccharide (E. coli LPS; 50 ng/kg; iv) treated horses. W...
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...
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 ...
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...
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...
