scholarly journals Investigation of Synovial Fluid Lubricants and Inflammatory Cytokines in the Horse: a Comparison of Recombinant Equine Interleukin 1β-induced Synovitis and Joint Lavage Models

Author(s):  
Amanda Watkins ◽  
Diana Fasanello ◽  
Darko Stefanovski ◽  
Sydney Schurer ◽  
Katherine Caracappa ◽  
...  

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.

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Amanda Watkins ◽  
Diana Fasanello ◽  
Darko Stefanovski ◽  
Sydney Schurer ◽  
Katherine Caracappa ◽  
...  

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.


2013 ◽  
Vol 7 (1) ◽  
pp. 378-384 ◽  
Author(s):  
Heather K Vincent ◽  
Susan S Percival ◽  
Bryan P Conrad ◽  
Amanda N Seay ◽  
Cindy Montero ◽  
...  

Objective: This study examined the changes in synovial fluid levels of cytokines, oxidative stress and viscosity six months after intraarticular hyaluronic acid (HA) treatment in adults and elderly adults with knee osteoarthritis (OA). Design: This was a prospective, repeated-measures study design in which patients with knee OA were administered 1% sodium hyaluronate. Patients (N=28) were stratified by age (adults, 50-64 years and elderly adults, ≥65 years). Ambulatory knee pain values and self-reported physical activity were collected at baseline and month six. Materials and Methods: Knee synovial fluid aspirates were collected at baseline and at six months. Fluid samples were analyzed for pro-inflammatory cytokines (interleukins 1β, 6,8,12, tumor necrosis factor-α, monocyte chemotactic protein), anti-inflammatory cytokines (interleukins 4, 10 13), oxidative stress (4-hydroxynonenal) and viscosity at two different physiological shear speeds 2.5Hz and 5Hz. Results: HA improved ambulatory knee pain in adults and elderly groups by month six, but adults reported less knee pain-related interference with participation in exercise than elderly adults. A greater reduction in TNF-α occurred in adults compared to elderly adults (-95.8% ± 7.1% vs 19.2% ± 83.8%, respectively; p=.044). Fluid tended to improve at both shear speeds in adults compared to the elderly adults. The reduction in pain severity correlated with the change in IL-1β levels by month six (r= -.566; p=.044). Conclusion: Reduction of knee pain might be due to improvements in synovial fluid viscosity and inflammation. Cartilage preservation may be dependent on how cytokine, oxidative stress profiles and viscosity change over time.


2009 ◽  
Vol 132 (1) ◽  
Author(s):  
Miroslav Hlaváček

Human ankle joint lubrication in walking is analyzed. A biphasic mixture model is considered for articular cartilage (ideal interstitial fluid and elastic porous matrix that is transversely isotropic and inhomogeneous throughout its thickness). Synovial fluid is considered Newtonian. Its viscosity is due to the macromolecules of hyaluronic acid that are too large to enter the matrix pores. Due to the fluid pressure gradient water and small solutes pass through the matrix pores and across the articular surface in both directions. The effect of the time varying concentration of hyaluronic acid or of the synovial fluid viscosity on the synovial film thickness distribution is small and neglected in the model. Periodic sliding motion of the articular surfaces and periodic loading of the joint as encountered in walking are included in the analysis. Synovial fluid serves as a fluid lubricant. The model shows that soon after the onset of walking the normal human ankle joint works in a mixed lubrication mode (a combination of boundary and fluid-film lubrications). A protective gel layer formed in the gap due to the synovial fluid filtration by cartilage may serve as a boundary lubricant. The synovial gel layer is not guaranteed in the osteoarthritic case, and the rough sliding surfaces may get repeatedly into an intimate contact and wear off due to the reciprocating sliding motion.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Diana C. Fasanello ◽  
Jin Su ◽  
Siyu Deng ◽  
Rose Yin ◽  
Marshall J. Colville ◽  
...  

Abstract Background TNF-α-stimulated gene 6 (TSG-6) protein, a TNF-α-responsive hyaladherin, possesses enzymatic activity that can catalyze covalent crosslinks of the polysaccharide hyaluronic acid (HA) to another protein to form heavy chain-hyaluronic acid (HC-HA) complexes in pathological conditions such as osteoarthritis (OA). Here, we examined HA synthase and inflammatory gene expression; synovial fluid HA, TNF-α, and viscosity; and TSG-6-mediated HC-HA complex formation in an equine OA model. The objectives of this study were to (1) evaluate the TNF-α-TSG-6-HC-HA signaling pathway across multiple joint tissues, including synovial membrane, cartilage, and synovial fluid, and (2) determine the impact of OA on synovial fluid composition and biophysical properties. Methods HA and inflammatory cytokine concentrations (TNF-α, IL-1β, CCL2, 3, 5, and 11) were analyzed in synovial fluid from 63 OA and 25 control joints, and HA synthase (HAS1-3), TSG-6, and hyaluronan-degrading enzyme (HYAL2, HEXA) gene expression was measured in synovial membrane and cartilage. HA molecular weight (MW) distributions were determined using agarose gel electrophoresis and solid-state nanopore measurements, and HC-HA complex formation was detected via immunoblotting and immunofluorescence. SEC-MALS was used to evaluate TSG-6-mediated HA crosslinking, and synovial fluid and HA solution viscosities were analyzed using multiple particle-tracking microrheology and microfluidic measurements, respectively. Results TNF-α concentrations were greater in OA synovial fluid, and TSG6 expression was upregulated in OA synovial membrane and cartilage. TSG-6-mediated HC-HA complex formation was greater in OA synovial fluid and tissues than controls, and HC-HA was localized to both synovial membrane and superficial zone chondrocytes in OA joints. SEC-MALS demonstrated macromolecular aggregation of low MW HA in the presence of TSG-6 and inter-α-inhibitor with concurrent increases in viscosity. Conclusions Synovial fluid TNF-α concentrations, synovial membrane and cartilage TSG6 gene expression, and HC-HA complex formation were increased in equine OA. Despite the ability of TSG-6 to induce macromolecular aggregation of low MW HA with resultant increases in the viscosity of low MW HA solutions in vitro, HA concentration was the primary determinant of synovial fluid viscosity rather than HA MW or HC-HA crosslinking. The TNF-α-TSG-6-HC-HA pathway may represent a potential therapeutic target in OA.


2021 ◽  
Vol 179 (6) ◽  
pp. 94-100
Author(s):  
V. E. Fedorov ◽  
N. B. Zakharova ◽  
O. E. Logvina

At present, the determination of the severity of patients with complications of acute calculous cholecystitis, manifested in the form of mechanical jaundice (MJ), remains an insufficiently studied issue. This is due to the fact that the main attention in the examination of such patients is paid to the diagnosis and assessment of the severity of liver failure, and the signs of SIRS (Systemic Inflammatory Response Syndrome) are not given due attention. In this regard, this literature review presents data on the systemic inflammatory response syndrome in such patients, describes its etiopathogenetic mechanisms of development, presents clinical signs, stages of this pathological process. The role of biomarkers, which can be used to determine the severity of inflammatory changes in the biliary system in MJ, is estimated on the basis of literature data.


2017 ◽  
Vol 40 (5) ◽  
pp. 205-211 ◽  
Author(s):  
Khosrow S. Houschyar ◽  
Malcolm N. Pyles ◽  
Susanne Rein ◽  
Ina Nietzschmann ◽  
Dominik Duscher ◽  
...  

Sepsis is a well-recognized healthcare issue worldwide, ultimately resulting in significant mortality, morbidity and resource utilization during and after critical illness. In its most severe form, sepsis causes multi-organ dysfunction that produces a state of critical illness characterized by severe immune dysfunction and catabolism. Sepsis induces the activation of complement factor via 3 pathways and the release of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β), resulting in a systemic inflammatory response. The inflammatory cytokines and nitric oxide release induced by sepsis decrease systemic vascular resistance, resulting in profound hypotension. The combination of hypotension and microvascular occlusion results in tissue ischemia and ultimately leads to multiple organ failure. Several clinical and experimental studies have reported that treatment using adsorption of cytokines is beneficial during endotoxemia and sepsis. This review article analyzes the efficacy of CytoSorb® adsorber in reducing the inflammatory response during sepsis. The CytoSorb® adsorber is known to have excellent adsorption rates for inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-10, and TNF-α. Studies have demonstrated that treatment with cytokine adsorbing columns has beneficial effects on the survival rate and inflammatory responses in animal septic models. Additionally, several cases have been reported in which treatment with cytokine adsorbing columns is very effective in hemodynamic stabilization and in preventing organ failure in critically ill patients. Although further investigations and clinical trials are needed, treatment with cytokine adsorbing columns may play an important role in the treatment of sepsis in the near future.


2018 ◽  
Vol 24 (3) ◽  
pp. 341-358 ◽  
Author(s):  
Xiaotong Ji ◽  
Yingying Zhang ◽  
Guangke Li ◽  
Nan Sang

Recently, numerous studies have found that particulate matter (PM) exposure is correlated with increased hospitalization and mortality from heart failure (HF). In addition to problems with circulation, HF patients often display high expression of cytokines in the failing heart. Thus, as a recurring heart problem, HF is thought to be a disorder characterized in part by the inflammatory response. In this review, we intend to discuss the relationship between PM exposure and HF that is based on inflammatory mechanism and to provide a comprehensive, updated evaluation of the related studies. Epidemiological studies on PM-induced heart diseases are focused on high concentrations of PM, high pollutant load exposure in winter, or susceptible groups with heart diseases, etc. Furthermore, it appears that the relationship between fine or ultrafine PM and HF is stronger than that between HF and coarse PM. However, fewer studies paid attention to PM components. As for experimental studies, it is worth noting that coarse PM may indirectly promote the inflammatory response in the heart through systematic circulation of cytokines produced primarily in the lungs, while ultrafine PM and its components can enter circulation and further induce inflammation directly in the heart. In terms of PM exposure and enhanced inflammation during the pathogenesis of HF, this article reviews the following mechanisms: hemodynamics, oxidative stress, Toll-like receptors (TLRs) and epigenetic regulation. However, many problems are still unsolved, and future work will be needed to clarify the complex biologic mechanisms and to identify the specific components of PM responsible for adverse effects on heart health.


1970 ◽  
Vol 11 (2) ◽  
pp. 139-155 ◽  
Author(s):  
Nils W. Rydell ◽  
Judson Butler ◽  
Endre A. Balazs

2021 ◽  
pp. 155633162199200
Author(s):  
Ravi Gupta ◽  
Anil Kapoor ◽  
Sourabh Khatri ◽  
Dinesh Sandal ◽  
Gladson David Masih

Background: Osteoarthritis (OA) in the anterior cruciate ligament (ACL)–deficient knee is seen in approximately 50% of affected patients. Possible causes include biochemical or biomechanical changes. Purpose: We sought to study the correlation between inflammatory cytokines and chondral damage in ACL-deficient knees. Methods: Seventy-six male patients who underwent ACL reconstruction were enrolled in a cross-sectional study. Synovial fluid was aspirated before surgery and analyzed for levels of the inflammatory cytokines tumor necrosis factor-α, interleukin-1 (IL-1), and interleukin-6 (IL-6). At the time of ACL reconstruction, the severity of chondral damage was documented as described by the Outerbridge classification. Results: Patients with grade 2 or higher chondral damage were observed to have elevated IL-6 levels when compared to patients who had no chondral damage. Interleukin-6 levels had no correlation with the duration of injury. Conclusion: Elevated levels of IL-6 in synovial fluid were associated with chondral damage in ACL-deficient knees. Further study is warranted to determine whether inflammatory cytokines contribute to the development of OA of the knee after ACL injury.


Author(s):  
Judit Biosca-Brull ◽  
Cristian Pérez-Fernández ◽  
Santiago Mora ◽  
Beatriz Carrillo ◽  
Helena Pinos ◽  
...  

Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies.


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