Abstract
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.
Highlights
In 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
The clinical presentation in SIRS and sepsis is mainly caused by the immunological host response [2], which is orchestrated by highly dynamic and complex interactions of a vast number of cytokines, hormones, growth factors, and pattern recognition receptors derived from immunologically active cells, including leukocytes and endothelial cells [2, 3]
Fever peaked at postinduction hour (PIH) 4 and white blood cell count (WBC) and borborygmus started to increase
Summary
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. High mortality rates in the equine clinic are related to the development and progression of severe systemic inflammatory conditions like the systemic inflammatory response syndrome (SIRS) and sepsis. This is seen in diseases as metritis, colitis, small intestinal strangulation, large intestinal volvulus, pleuropneumonia, and intrauterine/neonatal infections [1]. An exact and timely status of an inflammatory condition is extremely difficult to obtain on the basis of clinical parameters, and insights into the early immunological disease processes may hold the key for future diagnostic and therapeutic advances in SIRS and sepsis
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