Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses

Tadros, Elizabeth M.; Frank, Nicholas

doi:10.2460/ajvr.73.9.1394

Cited by 41 publications

(38 citation statements)

References 52 publications

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“…These findings were in part similar to those obtained by other researchers (Tadros and Frank 2012). It was previously stated that the release of TNF-α from macrophages begins at 30 min after the initial exposure, suggesting that this mediator can be an early regulator of the immune response with subsequent release of an array of downstream immunoregulatory mediators.…”

Section: Discussionsupporting

confidence: 91%

The influence of experimentally-induced endotoxaemia on clinical variables and markers of systemic inflammation in donkeys (Equus asinus)

El-Ashker¹,

El-Sebaei²,

Aamer³

2017

Vet. Med. - Czech

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ABSTRACT:In view of the frequent involvement of endotoxins in the pathogenesis of equine diseases, the present study set out to gain preliminary insight into the challenge caused by lipopolysaccharide (LPS) exposure in donkeys and into the responses of animals to LPS challenge. To the best of our knowledge, this is the first study to determine the susceptibility and response of donkeys to LPS administration and the first to describe the extent to which donkeys can tolerate a state of endotoxaemia. For this purpose, 18 clinically healthy, native breed donkeys were randomly allocated into three groups of equal size. The first and second groups received E. coli O55:B5 endotoxin at a dose rate of 20 ng/kg (Low dose group), and 5.0 µg/kg (High dose group), respectively, after dilution in 500 ml of 0.9% normal saline, while the third group (Control) received 500 ml of 0.9% isotonic saline solution. Blood samples were drawn from each animal before exposure to LPS and hourly for 6 h subsequently to measure the circulating levels of inflammatory cytokines as well as the cellular response. All animals were clinically monitored throughout the study period. Following LPS exposure, donkeys in both treated groups had quite different temporal patterns of clinical manifestations. The high dose of LPS yielded a statistically significant (P < 0.001 and P < 0.001, respectively) increase in heart rate, and respiratory rate, as well as hypothermia and poor outcome compared with animals receiving the low dose. The severity of colic was, in general, mild in donkeys receiving the low dose of LPS, while the signs were overt in those receiving the high dose. Donkeys of both treated groups exhibited marked cellular alterations and up-regulation of tumour necrosis factor alpha, interleukin (IL)-12 and IL-10 with a marginal increase in the values of serum amyloid A compared with controls (P < 0.05). The results described herein demonstrate that donkeys can respond to even a physiological dose of E. coli O55:B5 endotoxin, while a high dose can elicit overt clinical alterations and marked inflammatory responses. Further studies with an extended follow-up time are needed to verify and generalise the obtained findings and to evaluate novel medications to minimise the deleterious consequences of endotoxaemia in equine patients.

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Section: Discussionsupporting

confidence: 91%

The influence of experimentally-induced endotoxaemia on clinical variables and markers of systemic inflammation in donkeys (Equus asinus)

El-Ashker¹,

El-Sebaei²,

Aamer³

2017

Vet. Med. - Czech

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“…The four-week washout was selected to eliminate possible effects of LPS tolerance [28, 29]. Before the study was initiated, all horses were trained with positive reinforcement to reduce the need for sedation during experimental procedures such as arthrocentesis, in order to minimize potential analgesic and anti-inflammatory effects of sedatives.…”

Section: Methodsmentioning

confidence: 99%

Changes in concentrations of haemostatic and inflammatory biomarkers in synovial fluid after intra-articular injection of lipopolysaccharide in horses

et al. 2017

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BackgroundSeptic arthritis is a common and potentially devastating disease characterized by severe intra-articular (IA) inflammation and fibrin deposition. Research into equine joint pathologies has focused on inflammation, but recent research in humans suggests that both haemostatic and inflammatory pathways are activated in the joint compartment in arthritic conditions. The aim of this study was to characterize the IA haemostatic and inflammatory responses in horses with experimental lipopolysaccharide (LPS)-induced joint inflammation. Inflammation was induced by IA injection of LPS into one antebrachiocarpal joint of six horses. Horses were evaluated clinically with subjective grading of lameness, and blood and synovial fluid (SF) samples were collected at post injection hours (PIH) -120, −96, −24, 0, 2, 4, 8, 16, 24, 36, 48, 72 and 144. Total protein (TP), white blood cell counts (WBC), serum amyloid A (SAA), haptoglobin, iron, fibrinogen, thrombin-antithrombin (TAT) and d-dimer concentrations were assessed in blood and SF.ResultsIntra-articular injection of LPS caused local and systemic signs of inflammation including increased rectal temperature, lameness and increased joint circumference and skin temperature. Most of the biomarkers (TP, WBC, haptoglobin, fibrinogen and TAT) measured in SF increased quickly after LPS injection (at PIH 2–4), whereas SAA and d-dimer levels increased more slowly (at PIH 16 and 144, respectively). SF iron concentrations did not change statistically significantly. Blood WBC, SAA, haptoglobin and fibrinogen increased and iron decreased significantly in response to the IA LPS injection, while TAT and d-dimer concentrations did not change. Repeated pre-injection arthrocenteses caused significant changes in SF concentrations of TP, WBC and haptoglobin.ConclusionSimilar to inflammatory joint disease in humans, joint inflammation in horses was accompanied by an IA haemostatic response with changes in fibrinogen, TAT and d-dimer concentrations. Inflammatory and haemostatic responses were induced simultaneously and may likely interact. Further studies of interactions between the two responses are needed for a better understanding of pathogenesis of joint disease in horses. Knowledge of effects of repeated arthrocenteses on levels of SF biomarkers may be of value when markers are used for diagnostic purposes.

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“…In foals, several studies have been conducted comparing innate gene expressions in blood leukocytes in septic patients versus non-septic [7–9] and healthy foals [10, 11]. In adult horses leukocyte immune genes have been correlated to type of disease and outcome in patients with gastrointestinal inflammation and strangulation [12] while a small number of studies have had a primary aim of investigating leukocyte innate immune gene expressions in experimental lipopolysaccharide- (LPS-) induced systemic inflammation [13–15]. These studies all encourage further investigations of the diagnostic potential of the immunological disease processes in equine systemic inflammation.…”

Section: Introductionmentioning

confidence: 99%

Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

et al. 2015

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BackgroundIn horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic inflammation was induced in 6 adult horses by the intravenous injection of 1 μg lipopolysaccharide (LPS) per kg btw. Sixteen blood samples were collected for each horse at predetermined intervals and analyzed by reverse transcription quantitative real-time PCR. Post-induction expression levels for each gene were compared with baseline levels.ResultsSystemic inflammation was confirmed by the presence of clinical and hematological changes which were consistent with SIRS. The clinical response to LPS was transient and brief as all horses except one showed unaltered general demeanor after 24 h. Twenty-two leukocyte genes were significantly regulated at at least one time point during the experimental period. By close inspection of the temporal responses the dynamic changes in mRNA abundance revealed a very rapid onset of both pro- and anti-inflammatory mediators and a substantial variation in both expression magnitudes and duration of changes between genes. A majority of the 22 significantly regulated genes peaked within the first 8 h after induction, and an on-going, albeit tightly controlled, regulation was seen after 24 h despite approximate clinical recovery.ConclusionsThis first broad study of gene expressions in blood leukocytes during equine acute LPS-induced systemic inflammation thoroughly characterized a highly regulated and dynamic innate immune response. These results provide new insights into the molecular mechanisms of equine systemic inflammation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-015-0450-5) contains supplementary material, which is available to authorized users.

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Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses

Abstract: Horses developed LPS tolerance within approximately 24 hours after administration was started, and the method of LPS administration did not affect the magnitude or duration of systemic inflammation. Laminitis was not induced in horses.

Cited by 41 publications

References 52 publications

The influence of experimentally-induced endotoxaemia on clinical variables and markers of systemic inflammation in donkeys (Equus asinus)

The influence of experimentally-induced endotoxaemia on clinical variables and markers of systemic inflammation in donkeys (Equus asinus)

Changes in concentrations of haemostatic and inflammatory biomarkers in synovial fluid after intra-articular injection of lipopolysaccharide in horses

Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

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