Investigation of synovial fluid lubricants and inflammatory cytokines in the horse: a comparison of recombinant equine interleukin 1 beta-induced synovitis and joint lavage models

Abstract

Background Lameness is a debilitating condition in equine athletes that leads to more performance limitation and loss of use than any other medical condition. There are a limited number of non-terminal experimental models that can be used to study early inflammatory and synovial fluid biophysical changes that occur in the equine joint. Here, we compare the well-established carpal IL-1β-induced synovitis model to a tarsal intra-articular lavage model, focusing on serial changes in synovial fluid inflammatory cytokines/chemokines and the synovial fluid lubricating molecules lubricin/proteoglycan 4 and hyaluronic acid. The objectives of this study were to evaluate clinical signs; synovial membrane and synovial fluid inflammation; and synovial fluid lubricants and biophysical properties in response to carpal IL-1β synovitis and tarsal intra-articular lavage. Results Hyaluronic acid (HA) concentrations, especially high molecular weight HA, and synovial fluid viscosity decreased after both synovitis and lavage interventions. Synovial fluid lubricin concentrations increased 17–20-fold for both synovitis and lavage models, with similar changes in both affected and contralateral joints, suggesting that repeated arthrocentesis alone resulted in elevated synovial fluid lubricin concentrations. Synovitis resulted in a more severe inflammatory response based on clinical signs (temperature, heart rate, respiratory rate, lameness and joint effusion) and clinicopathological and biochemical parameters (white blood cell count, total protein, prostaglandin E2, sulfated glycosaminoglycans, tumor necrosis factor-α and CC chemokine ligands − 2, − 3, − 5 and − 11) as compared to lavage. Conclusions Synovial fluid lubricin increased in response to IL-1β synovitis and joint lavage but also as a result of repeated arthrocentesis. Frequent repeated arthrocentesis is associated with inflammatory changes, including increased sulfated glycosaminoglycan concentrations and decreased hyaluronic acid concentrations. Synovitis results in more significant inflammatory changes than joint lavage. Our data suggests that synovial fluid lubricin, TNF-α, CCL2, CCL3, CCL5, CCL11 and sGAG may be useful biomarkers for synovitis and post-lavage joint inflammation. Caution should be exercised when performing repeated arthrocentesis clinically or in experimental studies due to the inflammatory response and loss of HA and synovial fluid viscosity.

Morphological and radiological study of the shoulder and elbow joints of the giant anteater (Myrmecophaga tridactyla)

“…The position of the needle is particularly important for this type of procedure, so as not to cause lesions in the adjacent tissues, such as arteries, vessels, or nerves, and to access the joint with minimal soft tissue damage. Arthrocentesis is a common intervention for diagnosis or treatment of joint diseases in veterinary practice in small animals and horses (Kearney et al, 2021; Lavallée et al, 2020; Mielke et al, 2018; Watkins et al, 2021). Synovial fluid collection for cytology, bacterial or fungal culture, arthrography, intra‐articular injections of medication such as corticosteroids and anesthetics are some of clinical applications of this procedure (Kearney et al, 2021; Lavallée et al, 2020; Mielke et al, 2018; Pouyet & Bonilla, 2021; Watkins et al, 2021; Whipple et al, 2019).…”

“…Arthrocentesis is a common intervention for diagnosis or treatment of joint diseases in veterinary practice in small animals and horses (Kearney et al, 2021; Lavallée et al, 2020; Mielke et al, 2018; Watkins et al, 2021). Synovial fluid collection for cytology, bacterial or fungal culture, arthrography, intra‐articular injections of medication such as corticosteroids and anesthetics are some of clinical applications of this procedure (Kearney et al, 2021; Lavallée et al, 2020; Mielke et al, 2018; Pouyet & Bonilla, 2021; Watkins et al, 2021; Whipple et al, 2019). Other procedures to treat joint diseases such as arthroscopy and arthrotomy can also be performed (Hoelzler et al, 2004; Pouyet & Bonilla, 2021), although for all these interventions it is necessary to know the normal anatomy of the joint to be accessed.…”

Targeted Analysis of the Size Distribution of Heavy Chain-Modified Hyaluronan with Solid-State Nanopores

“…Equine Synovitis Model Synovial Fluid Collection. SF samples were obtained as previously described 57 with protocol approval by the Cornell University IACUC (#2018-0024). Briefly a 20-year-old Mustang/Arabian cross mare was evaluated by 2 veterinarians and determined to have no preexisting lameness or joint effusion.…”

Effects of Intra-Articular Autologous Adipose Micrograft for the Treatment of Osteoarthritis in Dogs: A Prospective, Randomized, Controlled Study

“…After cytological assessment, the remaining synovial fluid aliquots, obtained from dogs sampled at T0, T1, and T2, were used to evaluate the concentration of three cytokines (TNFα, IL-6, and IL-1β) through Nori ® canine ELISA kits (Genorise Scientific Inc., Glen Mills, PA, USA), according to the manufacturer’s protocols. These three biomarkers were chosen based on previous literature supporting the constant presence of these three cytokines and their concentration as relating to OA severity [ 43 , 44 , 45 , 46 , 47 ]. In our study, each aliquot of synovial fluid was used first for TNF-α evaluation and subsequently for IL-6 and IL-1β.…”