Expression of inflammation-associated genes in circulating leukocytes collected from horses with gastrointestinal tract disease

Lopes, Marco A. F.; Salter, Caroline E.; Vandenplas, Michel L.; Berghaus, Roy D.; Hurley, David J.; Moore, James N.

doi:10.2460/ajvr.71.8.915

Cited by 16 publications

(14 citation statements)

References 72 publications

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“…Circulating cytokines TNF-a, IL-1, IL-6, IL-8, and MCP-1 (CCL2) in humans are associated with a prothrombotic state, [8][9][10] and whereas an activated coagulation and/or increased DD concentrations were found during severe gastrointestinal, ischemic disorders in horses, Lopes et al successfully detected mRNA up-regulation of TNF-a, IL-1RA, IL-6, and IL-8 in PBMC under similar conditions of gastrointestinal disease. 6,21,22 Furthermore, TNF-a concentration increases in plasma and abdominal fluids from horses with these conditions have also been detected. 23,24 Although these results suggest that there is evidence of concurrent cytokine and DD production, it is possible that DD production in horses/ponies during EHV-1 viremia is also cytokine-driven.…”

Section: Discussionmentioning

confidence: 94%

Plasma D‐Dimer Concentrations during ExperimentalEHV‐1 Infection of Horses

Goehring

Hussey

Díez

et al. 2013

Veterinary Internal Medicne

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Background: Central nervous system blood vessel thrombosis is a part of the pathogenesis of equid herpesvirus-associated myeloencephalopathy (EHM). D-dimers (DD) are stable breakdown products of cross-linked fibrin, and increased DD-plasma concentrations could reflect the degree of systemic coagulation during EHV-1 infection.Hypothesis: We hypothesized that blood DD concentrations will be increased during periods of EHV-1 fever and viremia, reflecting an activated coagulation cascade with fibrinolysis.Animals: Twenty-eight equids were infected with EHV-1 in 3 experimental infection studies. Three (uninfected) horses were included in a separate study to evaluate methodology for DD concentration measurements.Methods: Clinical data and quantitative viremia were evaluated, and DD concentrations were measured in blood samples on the day before the infection and during days 1-12 postchallenge. Uninfected horses were sampled every 3 hours for 48 hours. Logistic and linear regression was used to investigate the potential association between the fever and viremia with the presence or absence of DD concentrations in peripheral blood.Results: DD concentrations were increased for 1-8 days in the majority of infected animals. Both viremia (odds ratio [OR] 6.3; 95% confidence interval [CI] 3.4-11.8; P = .0013) and fever (OR 4.9; CI 2.3-10.1; P = .001) were strongly associated with the likelihood of detecting DD in peripheral blood.Conclusions and Clinical Importance: EHV-1 viremia is associated with increases in DD concentration in horses and ponies. This indicates that EHV-1 viremia can lead to an activation of coagulation and fibrinolysis.

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Section: Discussionmentioning

confidence: 94%

Plasma D‐Dimer Concentrations during ExperimentalEHV‐1 Infection of Horses

Goehring

Hussey

Díez

et al. 2013

Veterinary Internal Medicne

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“…2010) and systemically in common inflammatory diseases of the horse (Nieto et al . 2009; Lopes et al . 2010; Peiro et al .…”

Section: Discussionmentioning

confidence: 99%

“…TNF is an important inflammatory mediator and increased concentrations have been detected locally in inflamed equine synovial tissue (Kamm et al 2010) and systemically in common inflammatory diseases of the horse (Nieto et al 2009;Lopes et al 2010;Peiro et al 2010). Human platelets and platelet-derived microparticles constitutively express TNF receptors I and II, and upregulation of the receptors has been observed when platelets are activated (Limb et al 1999;Baj-Krzyworzeka et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Stimulus‐dependent release of tissue‐regenerating factors by equine platelets

Dunkel¹,

Bolt²,

Smith³

et al. 2011

Equine Veterinary Journal

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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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Expression of inflammation-associated genes in circulating leukocytes collected from horses with gastrointestinal tract disease

Abstract: Inflammatory gene expression in leukocytes of horses with GIT disease appeared to be related to disease pathogenesis and prognosis.

Cited by 16 publications

References 72 publications

Plasma D‐Dimer Concentrations during ExperimentalEHV‐1 Infection of Horses

Plasma D‐Dimer Concentrations during ExperimentalEHV‐1 Infection of Horses

Stimulus‐dependent release of tissue‐regenerating factors by equine platelets

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

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