Hematologic, prostaglandin F_2α‐metabolite, serum amyloid A, and serum iron changes in horses with experimentally induced endotoxemia

Abstract

Background: 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. Objectives: 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 2α-metabolite (PGM), serum amyloid A (SAA), and serum total iron concentrations were monitored for up to 3 or 6 days. Results: An immediate and severe decrease in neutrophils and monocytes occurred in all horses, which subsequently changed to a moderate to strong neutrophilia and monocytosis that persisted for more than 78 hours postinfusion (PI) of LPS. Lymphocyte and eosinophil numbers decreased gradually and then normalized after 66-and 78-hours PI, respectively. Mild to moderate, biphasic thrombocytopenia occurred. A pronounced, transient increase in PGM occurred between 1 and 7 hours, peaking at 2 hours. Serum amyloid A began to increase after 6 hours PI and remained elevated after 72 hours PI. Serum iron was decreased between 6 and 48 hours. The clinical signs were most prominent during the first 24 hours PI and subsided within 48 hours PI. Conclusions: Neutrophilia, monocytoses, and high SAA concentrations were present in horses even after the clinical signs had subsided. Serum iron normalized before SAA. Knowledge of these findings is imperative when interpreting laboratory results in horses with possible endotoxin exposure.

Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia

“…Whereas there were no significant differences in SAA concentrations between treatment groups, SAA concentrations rose substantially to greater than 150 μg/mL 10 hours after LPS exposure, and >500 μg/mL 24 hours after LPS exposure, for all treatments. The timing of this increase is similar to other reports, where SAA concentrations rose significantly above baseline at 6 hours after LPS exposure and were >1000 μg/mL at 24 hours after LPS exposure 40 . This finding is indicative of the activation of the acute phase response under a transient sterile inflammatory state and underscores the importance of accurate interpretation of SAA in horses.…”

“…The timing of this increase is similar to other reports, where SAA concentrations rose significantly above baseline at 6 hours after LPS exposure and were >1000 μg/mL at 24 hours after LPS exposure. 40 This finding is indicative of the activation of the acute phase response under a transient sterile inflammatory state and underscores the importance of accurate interpretation of SAA in horses.…”

The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses

“…In addition to the SIRS/laminitis models above, the most common model for evaluation of the response of systemic inflammation to drug treatment in horses is the experimentally induced endotoxemia model. In this model, LPS (E. coli 055:B5) is administered intravenously (30-500 ng/kg), typically as a CRI over 0.5-6 h. Following LPS model induction, peak serum TNF-α concentrations are achieved within 1.5 h [34], neutropenia and leukopenia within 2-4 h [78], and peak fever response within 2-4 h and lasting up to 12 h [79]. The LPS model is reversible and at lower doses is not associated with long-term adverse effects.…”

“…However, it is important to note that SAA is a measure of the acute-phase (i.e., inflammatory) response, rather than a measure of specific etiology. SAA has been found to significantly increased in the sterile inflammatory state provoked following administration of LPS (E. coli O55:B5) [78]. Following administration of LPS, SAA was greater than 1000 mg/L at 23 h post-infusion and remained elevated for greater than 72 h post-LPS infusion [78].…”

“…SAA has been found to significantly increased in the sterile inflammatory state provoked following administration of LPS (E. coli O55:B5) [78]. Following administration of LPS, SAA was greater than 1000 mg/L at 23 h post-infusion and remained elevated for greater than 72 h post-LPS infusion [78].…”