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

Stine Mandrup Andreassen,Søren Saxmose Nielsen,Stine Jacobsen,Pia Haubro Andersen,Annemarie T Kristensen,Anne Mette Lindberg Vinther,Aziz Tnibar

doi:10.1186/s12917-017-1089-1

Stine Mandrup Andreassen, Søren Saxmose Nielsen + Show 5 more

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https://doi.org/10.1186/s12917-017-1089-1

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Abstract

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.

Highlights

Septic arthritis is a common and potentially devastating disease characterized by severe intra-articular (IA) inflammation and fibrin deposition
The horses were included if they were free of clinical signs of inflammation, and levels of inflammatory parameters (WBC and differential leukocyte count, serum amyloid A (SAA), iron, fibrinogen) in blood were within reference ranges
Post-injection period: clinical parameters The IA injection of LPS induced lameness starting at post injection hours (PIH) 2, which resolved around PIH 48

Summary

Introduction

Septic arthritis is a common and potentially devastating disease characterized by severe intra-articular (IA) inflammation and fibrin deposition. 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. Research into the pathogenesis of arthritis in horses has focused on inflammation in IA tissues, diagnostic assessment of inflammatory markers such as white blood cell counts (WBC), total protein (TP), serum amyloid A (SAA), pro-inflammatory cytokines, and eicosanoids in synovial fluid (SF), and on measures to control inflammation [5,6,7,8,9]. In non-inflamed SF from humans fibrinogen was absent or found in very low levels [13, 17], and in inflammatory joint conditions, such as RA, osteoarthritis (OA) and antigen-induced arthritis, increased SF fibrinogen concentration has been demonstrated [17,18,19]. Fibrinogen is an acute phase reactant, and similar to other acute phase reactants, such as SAA, haptoglobin and iron, plasma concentrations of fibrinogen will change in response to inflammatory and infectious conditions [22]

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