Synovial Interleukin-6 Research Articles

Evaluation of interleukin-6 in synovial fluid in periprosthetic joint infection of the elbow.

Searching for quick determinable biomarkers with high sensitivity and specificity is necessary to improve and optimise the early diagnosis of periprosthetic elbow infection (PEI). Therefore, this study's objective was to evaluate the diagnostic value of synovial fluid interleukin-6 (IL-6) levels for diagnosing PEI in total elbow arthroplasty. Twelve prospective enrolled patients underwent total elbow arthroplasty revision surgery, during which synovial fluid was obtained. Between the initial implantation and the revision procedure were 33.5 ± 41months (range, 2-144months). Synovial fluid was collected for immediate IL-6 analysis parallel to the revision surgery. Furthermore, microbiological samples were obtained and analysed. Two groups were defined based on the microbiological results: non-infection and infection group. The ability of synovial fluid IL-6 analysis to predict infection status was explored using receiver operating characteristic curves and further statistical analysis. Synovial fluid IL-6 analysis had a good diagnostic accuracy of 83% for PEI with an area under the curve of 0,79 and an ideal cutoff value (determined using Youden's criterion) of 15244pg/mL. This is the first study to clinically evaluate IL-6 as a diagnostical marker for periprosthetic joint infection (PJI) in total elbow arthroplasty. Our results suggest a good accuracy and high sensitivity for IL-6 to identify a PEI. The analysis of IL-6 can improve surgical decision-making regarding managing total elbow arthroplasty in terms of one- or two-staged revision. IL-6 can play an important role in the perioperative differentiation of infected and non-infected situations.

Early effectiveness of local injection of multimodal drug cocktail during anterior cruciate ligament reconstruction and its influence on cartilage

To explore the early effectiveness and influence on cartilage of local injection of multimodal drug cocktail (MDC) during anterior cruciate ligament reconstruction (ACLR). Between February 2022 and August 2023, patients undergone arthroscopic ACLR using autologous hamstring tendons were selected as the study subjects. Among them, 90 patients met the selection criteria and were randomly divided into 3 groups ( n=30) according to the different injection drugs after ligament reconstruction. There was no significant difference in baseline data such as gender, age, body mass index, surgical side, disease duration, preoperative thigh circumference, and preoperative levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1, matrix metalloproteinase 3 (MMP-3), MMP-13, and aggrecan (ACAN) in synovial fluid between groups ( P>0.05). After the ligament reconstruction during operation, corresponding MDC (consisting of ropivacaine, tranexamic acid, and betamethasone in group A, and ropivacaine, betamethasone, and saline in group B) or saline (group C) were injected into the joint and tendon site, respectively. The length of hospital stay, postoperative tramadol injection volume, incidence of complications, degree of knee joint swelling and range of motion, visual analogue scale (VAS) score, International Knee Documentation Committee (IKDC) score, Lyshlom score, and Hospital for Special Surgery (HSS) score were recorded and compared between groups. The T2 * values in different cartilage regions were detected by MRI examination and the levels of TNF-α, IL-6, IL-1, MMP-3, MMP-13, and ACAN in synovial fluid were detected by ELISA method. The patients in group A, B, and C were followed up (12.53±3.24), (13.14±2.87), and (12.82±3.32) months, respectively. All incisions healed by first intention. Compared with group C, group A and group B had shorter length of hospital stay, less tramadol injection volume, and lower incidence of complications, showing significant differences ( P<0.05); there was no significant difference between group A and group B ( P>0.05). The degree of knee swelling in group A was significantly less than that in group B and group C ( P<0.05), but there was no significant difference between group B and group C ( P>0.05). At 3, 6, 12, 24, and 48 hours after operation, VAS scores of group A and group B were significantly lower than those of group C ( P<0.05); at 72 hours after operation, there was no significant difference among the three groups ( P>0.05). At 3 days, 14 days, and 1 month after operation, the range of motion of knee joint in group A were significantly better than those in group C ( P<0.05), and there was no significant difference between the other groups ( P>0.05). At 1 month after operation, the IKDC score of group A and group B was significantly higher than that of group C ( P<0.05); there was no significant difference among the three groups at other time points ( P>0.05). There was no significant difference in Lyshlom score and HSS score among the three groups at each time point ( P>0.05). At 14 days after operation, the levels of IL-1 and IL-6 in the synovial fluid in groups A and B were significantly lower than those in group C ( P<0.05). There was no significant difference in the levels of TNF-α, MMP-3, MMP-13, and ACAN between groups A and B ( P>0.05). At 1 month after operation, there was no significant difference in the above indicators among the three groups ( P>0.05). At 3, 6, and 12 months after operation, there was no significant difference in the T2 * values of different cartilage regions among the three groups ( P>0.05). Injecting MDC (ropivacaine, tranexamic acid, betamethasone) into the joint and tendon site during ACLR can achieve good early effectiveness without significant impact on cartilage.

Relations between Structure/Composition and Mechanics in Osteoarthritic Regenerated Articular Tissue: A Machine Learning Approach.

In the context of a large animal model of early osteoarthritis (OA) treated by orthobiologics, the purpose of this study was to reveal relations between articular tissues structure/composition and cartilage viscoelasticity. Twenty-four sheep, with induced knee OA, were treated by mesenchymal stem cells in various preparations-adipose-derived mesenchymal stem cells (ADSCs), stromal vascular fraction (SVF), and amniotic endothelial cells (AECs)-and euthanized at 3 or 6 months to evaluate the (i) biochemistry of synovial fluid; (ii) histology, immunohistochemistry, and histomorphometry of articular cartilage; and (iii) viscoelasticity of articular cartilage. After performing an initial analysis to evaluate the correlation and multicollinearity between the investigated variables, this study used machine learning (ML) models-Variable Selection Using Random Forests (VSURF) and Extreme Gradient Boosting (XGB)-to classify variables according to their importance and employ them for interpretation and prediction. The experimental setup revealed a potential relation between cartilage elastic modulus and cartilage thickness (CT), synovial fluid interleukin 6 (IL6), and prostaglandin E2 (PGE2), and between cartilage relaxation time and CT and PGE2. SVF treatment was the only limit on the deleterious OA effect on cartilage viscoelastic properties. This work provides indications to future studies aiming to highlight these and other relationships and focusing on advanced regeneration targets.

Interleukin-6 in Synovial Fluid as a Tool for Differentiation of Inflammation and Degeneration in Chronic Synovitis and Treatment Selection

Interleukin-6 in Synovial Fluid as a Tool for Differentiation of Inflammation and Degeneration in Chronic Synovitis and Treatment Selection

Association of Dipeptidylpeptidase 4 (CD26) With Chondrocyte Senescence and Radiographic Progression in Knee Osteoarthritis.

To evaluate the association of dipeptidylpeptidase 4 (DPP-4; also known as CD26) with cellular senescence of human cartilage and progression of knee osteoarthritis (OA). Articular cartilage sections and chondrocytes were acquired from 35 individuals undergoing total knee replacement for OA to evaluate the following: 1) the association between OA severity and established senescence markers (senescence-associated β-galactosidase activity and p16), which was quantified using immunohistochemistry and flow cytometry (n=19 samples); 2) the coexpression of DPP-4 with established senescence markers, which was assessed using flow cytometry; and 3) expression levels of anabolic and catabolic genes, senescence-related genes, and senescence-associated secretory phenotypes in DPP-4+ and DPP-4- cells, which were isolated using fluorescence-activated cell sorting or magnetic-activated cell sorting (n=16 samples). The concentration of soluble DPP-4 was measured in samples of synovial fluid and samples of plasma from the Prediction of Osteoarthritis Progression cohort and then evaluated for association with the severity of radiographic knee OA at baseline (n=65 samples) and the progression of structural radiographic OA (n=57 samples) over a 3-year period. DPP-4 expression was associated with higher senescence-associated β-galactosidase activity, p16 expression, senescence-related gene and catabolic gene (ADAMTS5, MMP13, IL6, and IL8) expression, higher senescence-associated secretory phenotype secretion, and lower anabolic gene (COL2A1 and ACAN) expression in primary chondrocytes. Synovial fluid DPP-4 concentration was associated with radiographic OA progression (odds ratio 105.32; P=0.015), proteases (synovial fluid matrix metalloproteinase 1 and matrix metalloproteinase 3), aggrecan degradation (synovial fluid sulfated glycosaminoglycan), indicators of activated macrophages (synovial fluid CD14 and CD163), and inflammation (synovial fluid interleukin-6). Our study identifies DPP-4 as a key surface marker in senescent chondrocytes and a predictor of radiographic OA progression.

Serum and synovial Interleukin–17A level in Rheumatoid arthritis patients and its relation to disease activity

Serum and synovial Interleukin–17A level in Rheumatoid arthritis patients and its relation to disease activity

The Ratio of IL-6 to IL-4 in Synovial Fluid of Knee or Hip Performances a Noteworthy Diagnostic Value in Prosthetic Joint Infection.

The diagnosis of prosthetic joint infection (PJI) is still a challenge, the ratio of interleukin-6 (IL-6) to IL-4 in the joint fluid of knee or hip was used to analyze whether the diagnostic accuracy of PJI can be improved. Between January 2017 and May 2022, 180 patients who developed pain after revision total hip or knee arthroplasty were enrolled retrospectively. 92 patients of PJI and 88 of aseptic failure were included. PJI was as defined by the Musculoskeletal Infection Society (MSIS). The content of IL-6 and IL-4 in synovial fluid of knee or hip were measured, and the areas under the receiver operating characteristic curve (ROC) and IL-6/IL-4 curve were analyzed to obtain a better diagnostic effect. The area under the curve of IL-6/IL-4 in synovial fluid of knee or hip was 0.9623, which was more accurate than ESR 0.5994 and C-reactive protein 0.6720. The optimal threshold of IL-6/IL-4 ratio was 382.10. Its sensitivity and specificity were 81.32% and 98.86%, respectively. The positive predictive value for the diagnosis of PJI was 98.91%. This study showed that the level of IL-6/IL-4 in synovial fluid of knee or hip could further improve the diagnostic accuracy for PJI.

Fibrosis in frozen shoulder: Activation of IL-6 through PI3K-Akt signaling pathway in synovial fibroblast

Fibrosis is the main cause of limited range of motion (ROM) of shoulder in patients with frozen shoulder (FS). Overexpression of Interleukin 6 (IL-6) has been correlated with pathogenesis of FS. However, the underlying mechanism remains largely unexplored. In the current study, we focused on isolating synovial fibroblasts of FS and determining the influence of IL-6 as well as PI3K-Akt signaling pathway on the fibrotic process of synovial fibroblasts in FS by using RNA Sequencing (RNA-seq) and other molecular biology techniques. Synovial fibroblasts of FS express more extra cellular matrix (ECM) than that of control. RNA-seq results and bioinformatic analysis indicate that PI3K-Akt signaling pathway play an important role in the fibrotic process of FS, and IL-6 is the most related gene among those related to this process. The expression levels of IL-6 / IL-6R in FS synovial fibroblasts and IL-6 in culture supernatant were both significantly increased. siRNA interference with the expression of IL-6 attenuates the fibrosis level of FS as well as phosphorylation level of Akt. The findings suggest that synovial fibroblasts are key effector cells of fibrosis of FS. Activation of PI3K-Akt pathway can promote fibrosis of synovial fibroblasts in FS. IL-6 is up-regulated in synovial fibroblasts of FS and promoted the FS fibrosis through PI3K-Akt signaling pathway.

Synovial Fluid Interleukin Levels Cannot Distinguish between Prosthetic Joint Infection and Active Rheumatoid Arthritis after Hip or Knee Arthroplasty.

Inflammatory arthritis affects the level of synovial inflammatory factors, which makes it more difficult to diagnose prosthetic joint infection (PJI) patients with inflammatory arthritis. The aim of this study was to analyze synovial interleukin levels to distinguish between PJI and active rheumatoid arthritis (RA) after a hip or knee arthroplasty. From September 2019 to September 2021, we prospectively enrolled patients with joint pain after arthroplasty due to aseptic prosthesis loosening (n = 39), acute RA (n = 26), and PJI (n = 37). Synovial fluid from the affected joint is obtained and tested with a standard enzyme-linked immunosorbent assay. Receiver operating characteristic curve (ROC) was analyzed for each biomarker. Interleukin (IL)-1β, IL-6, and IL-8 showed promising value in differentiating of aseptic loosening from PJI, with areas under the curves (AUCs) of 0.9590, 0.9506, and 0.9616, respectively. Synovial IL-1β, IL-6, and IL-8 showed limited value in distinguishing between PJI and acute episodes of RA after arthroplasty, with AUCs of 0.7507, 0.7069, and 0.7034, respectively. Interleukins showed satisfactory efficacy in differentiating aseptic loosening from PJI. However, when pain after arthroplasty results from an acute episode of RA, current synovial interleukin levels do not accurately rule out the presence of PJI.

Serum and Synovial Biomarkers for Distinguishing Between Chronic Periprosthetic Joint Infections and Rheumatoid Arthritis: A Prospective Cohort Study.

Inflammatory responses in patients with active rheumatoid arthritis (RA) may lead to the current serum and synovial fluid biomarkers that misidentify chronic periprosthetic joint infection (PJI). We sought to investigate the expression of serum and synovial biomarkers in patients with active RA and to calculate thresholds for valuable biomarkers that distinguish between chronic PJI and active RA. This prospective study was initiated to enroll 70 patients undergoing revision arthroplasty from January 2019 to January 2021, and 30 patients with active RA cumulative knee from August 2020 to March 2021. The Musculoskeletal Infection Society definition of PJI was utilized for the classification of cases as aseptic or infected. Serum d-dimer, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 (IL-6), as well as synovial IL-6, percentage of polymorphonuclear neutrophils, and CD64 index level were measured preoperatively. An increase in biomarker concentrations were observed in group C (active RA). Synovial fluid CD64 index exhibited good discriminatory power between group B (chronic PJI) and group C with an area under curve of 0.930. For the diagnosis of chronic PJI in the presence of active RA, the optimal threshold value of synovial CD64 index was 0.87, with a sensitivity of 82.86% and a specificity of 93.33%. Current serum biomarkers (erythrocyte sedimentation rate, C-reactive protein, IL-6, and d-dimer) did not apply to the diagnosis of suspected PJI with active RA. Fortunately, satisfactory results can be achieved by adjusting the threshold of synovial fluid biomarkers.

The relationship of C-reactive protein/interleukin-6 concentrations between serum and synovial fluid in the diagnosis of periprosthetic joint infection

BackgroundThe relationship of C-reactive protein (CRP)/interleukin-6 (IL-6) concentrations between serum and synovial fluid and whether synovial CRP/IL-6 testing in addition to serum CRP/IL-6 testing would result in a benefit in the diagnosis of periprosthetic joint infection (PJI) deserves to be investigated.MethodsFrom June 2016 to July 2019, 139 patients were included in the study. Synovial CRP and IL-6 were tested by ELISA. The serum CRP and IL-6 were obtained from medical records. The definition of PJI was based on the modified Musculoskeletal Infection Society (MSIS) criteria. The relationship of serum and synovial CRP and IL-6 and the value of each index in the diagnosis of PJI were evaluated.ResultsThe receiver operating characteristic (ROC) curves showed that synovial IL-6 had the highest area under the curve (AUC) at 0.935, which was followed by synovial CRP, serum IL-6 and serum CRP 0.861, 0.847 and 0.821, respectively. When combining serum CRP and synovial CRP to diagnose PJI, the AUC was 0.849, which was slightly higher than the result obtained when using serum CRP alone. In contrast, when combining serum IL-6 and synovial IL-6 to diagnose PJI, the AUC increased to 0.940, which was significantly higher than that obtained using serum IL-6 alone.ConclusionThe synovial IL-6 has the highest diagnostic accuracy for PJI. However, inferring the level of CRP/IL-6 in the synovial fluid from the serum level of CRP/IL-6 was not feasible. Synovial CRP testing did not offer an advantage when combined with an existing serum CRP result to diagnose PJI, while additional synovial IL-6 was worthy of testing even if there was an existing serum IL-6 result.

Alpha-defensins determination in different types of synovial fluid and parallel collected serum samples by ELISA

The study aims were to verify the serum (S) and synovial fluid (SF) reference intervals (RIs) for human neutrophil defensins (HNP1-3); measure S and SF defensin concentrations in different types of SF, including non-inflammatory, inflammatory non-pyogenic, inflammatory pyogenic, and hemorrhagic; and to compare the HNP1-3 concentrations in SF and S with those of other inflammatory biomarkers. SF and S samples were collected from 92 patients. HNP1-3 concentrations were determined using enzyme-linked immunosorbent assays; glucose, lactate, interleukin-6, and procalcitonin using an automatic analyzer; and presepsin using a Pathfast system. There were 61 non-inflammatory, 11 inflammatory non-pyogenic, 11 inflammatory pyogenic, and 9 hemorrhagic SF. Non-inflammatory SF was divided into non-inflammatory normal and non-inflammatory osteoarthritis. The former was used to estimate the HNP1-3 RI in SF and S. The estimated HNP1-3 RIs of SF and S were 12.47-437.42 mg/L and 5.45-44.75 µg/L, respectively. HNP1-3 differed significantly between S and SF and individual groups of SF (P<0.001 and P=0.001, respectively). There were significant relationships between SF HNP1-3 and S HNP1-3 (P<0.001), S C-reactive protein (P<0.001), and S interleukin-6 (P=0.007), and between SF HNP1-3 and SF C-reactive protein (P=0.004) and SF interleukin-6 (P<0.001). The highest kappa coefficient was between SF HNP1-3 and SF interleukin-6 (κ=0.507). We validated the SF HNP1-3 diagnostic kit and demonstrated that SF and S HNP1-3 are promising biomarkers for distinguishing inflammatory from non-inflammatory joint diseases.

Interleukin-37 as an anti-inflammatory cytokine: does its relation to disease activity suggest its potential role in rheumatoid arthritis therapy?

BackgroundThis study aimed to measure the serum and synovial interleukin (IL)-37 levels in rheumatoid arthritis (RA) patients compared to patients with primary knee osteoarthritis (PKOA) and healthy controls and to detect its relation to RA disease activity.ResultsThis cross-sectional study included 50 RA patients with a mean age of 40.24 ± 8.62 years, 50 patients with PKOA with a mean age of 56.69 ± 4.21, and 40 healthy controls with a mean age of 41.75 ± 7.38 years. The mean serum IL-37 level in the RA patients (382.6 ± 73.97 pg/ml) was statistically significantly (P < 0.001) the highest among the studied groups; however, it showed a non-significant difference between the PKOA patients (70.38 ± 27.49 pg/ml) and the healthy controls (69.97 ± 25.12 pg/ml) (P > 0.94). Both serum and synovial IL-37 levels were significantly positively correlated with disease activity scores (r = 0.92, P< 0.001 and r = 0.85, P < 0.001), tender joint counts (r = 0.83, P < 0.001 and r = 0.82, P < 0.001 ), swollen joint counts (r = 0.72, P < 0.001 and r = 0.60, P < 0.001), visual analog scale (r = 0.82, P < 0.001 and r = 0.82, P < 0.001), erythrocyte sedimentation rate (r = 0.75, P < 0.001 and r = 0.65, P < 0.001), and C-reactive protein (r = 0.93, P < 0.001 and r = 0.79, P < 0.001), respectively.ConclusionSerum and synovial IL-37 were significantly elevated in the RA patients, and they were closely correlated. Being less invasive, the serum IL-37 could be a marker of disease activity and could reflect the effective disease control by drugs. Having an anti-inflammatory effect could not suggest IL-37 as the key player to control inflammation alone, but its combination with other anti-proinflammatory cytokines could be investigated.

There is an Association of Synovial Interleukin-6 Levels With Chondral Damage in Anterior Cruciate Ligament-Deficient Knees.

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.

Synovial fluid IL-1\u03b2 appears useful for the diagnosis of chronic periprosthetic joint infection

PurposeThe purpose of this study was to investigate the role of synovial fluid interleukin (IL)-1β in diagnosing chronic periprosthetic joint infection (PJI) and to identify the optimal threshold of synovial fluid IL-1β for differentiating chronic PJI from aseptic failure after knee and hip arthroplasties.MethodsBetween January 2019 and December 2019, we prospectively included patients scheduled to have a revision surgery for chronic PJI or aseptic failure after total joint arthroplasty. Then, synovial IL-1β was additionally measured along with routine preoperative diagnostic serum and synovial biomarkers. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker to determine diagnostic efficacy.ResultsOf the 93 patients included, their demographic data were not found to be statistically significant. The median synovial IL-1β levels were significantly higher in the chronic PJI group than in the aseptic group (894.73 pg/mL vs. 34.49 pg/mL, P<0.01). The AUC for synovial fluid IL-1β was 0.991, which was higher than serum ESR (0.627) and CRP (0.712). The optimal threshold value for detecting chronic PJI of synovial IL-1β was 312.7 pg/mL, with a sensitivity of 97.3% and a specificity of 94.64%. And the combined measurement of synovial fluid IL-1β and synovial fluid PMN% can led to a specificity of 1, and a negative predictive value (NPV) of 1.ConclusionsThe present study demonstrated that synovial fluid IL-1β is a valuable biomarker for detection of chronic PJI. The combination of synovial fluid IL-1β and PMN% led to an improvement in specificity compared with evaluation of each single index.Trial registrationThis study was prospectively registered on the Chinese Clinical Trial Registry (a non-profit organization, established according to both the WHO International Clinical Trials Register Platform Standard and Ottawa Group Standard), and the registering number was ChiCTR1800020440. Registered on December 29, 2018.

Management of Osteoarthritis Using 1 Intra-articular Platelet Concentrate Administration in a Canine Osteoarthritis Model

Background: Osteoarthritis (OA) represents a significant burden to societies, as it affects quality of life and performance and implies a large cost in terms of health care. Autologous platelets are a regenerative treatment modality for OA that are thought to be a potential stimulation of the natural healing cascade. Purpose: To describe the effect of the platelet concentrate V-PET in the management of OA in a naturally occurring canine model, using several outcome assessment modalities. Study Design: Controlled laboratory study. Methods: A total of 40 joints of active working police dogs with hip OA were randomly assigned to a control group (CG) and a platelet concentrate group (PCG; treatment) and evaluated. At treatment day (T0) and 8, 15, 30, 90, and 180 days after treatment, weight distribution, joint range of motion at flexion and extension, thigh girth, digital thermography, radiographic signs, 4 clinical metrology instruments, and synovial fluid interleukin 1 and C-reactive protein levels were recorded. Results were compared using repeated-measures analysis of variance with a Huynh-Feldt correction, paired-samples t test, or Wilcoxon signed rank test, with P < .05. Results: Dogs were 6.5 ± 2.4 years old (mean ± SD) and had a body weight of 26.7 ± 5.2 kg. At T0, 32 (80%) joints were graded as having mild OA, 6 (15%) as moderate, and 2 (5%) as severe. No differences were found between groups at T0. Between the PCG and CG, the symmetry index showed significant improvements in the PCG from 8 days (P = .01) to 180 days (P = .01). Joint flexion also improved in the PCG up to 90 days (P < .05) and extension improved up to 180 days (P < .01). Several clinical metrology instrument scores also improved up to 90 to 180 days after treatment. In the CG, radiographic signs progressed, while the PCG showed some improved signs. In both groups, increasing body weight and age corresponded with worse clinical and laboratory findings. Conclusion: A single injection of platelet concentrate had a positive effect, lasting up to 6 months, on several clinical, imaging, and laboratory signs in a naturally occurring canine OA model. Clinical Relevance: We characterized the effects of this platelet concentrate in dogs, considered the gold standard of the study of OA, with a group of working animals with similar high demands as athletes.

Synovial fluid interleukin-6 is not superior to cell count and differential in the detection of periprosthetic joint infection.

AimsSynovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells (%PMN) are elevated at periprosthetic joint infection (PJI). Leucocytes produce different interleukins (IL), including IL-6, so we hypothesized that synovial fluid IL-6 could be a more accurate predictor of PJI than synovial fluid WBC count and %PMN. The main aim of our study was to compare the predictive performance of all three diagnostic tests in the detection of PJI.MethodsPatients undergoing total hip or knee revision surgery were included. In the perioperative assessment phase, synovial fluid WBC count, %PMN, and IL-6 concentration were measured. Patients were labeled as positive or negative according to the predefined cut-off values for IL-6 and WBC count with %PMN. Intraoperative samples for microbiological and histopathological analysis were obtained. PJI was defined as the presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in a minimum of two or more samples out of at least four taken.ResultsIn total, 49 joints in 48 patients (mean age 68 years (SD 10; 26 females (54%), 25 knees (51%)) were included. Of these 11 joints (22%) were infected. The synovial fluid WBC count and %PMN predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 82%, 97%, 94%, 90%, and 95%, respectively. Synovial fluid IL-6 predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 73%, 95%, 90%, 80%, and 92%, respectively. A comparison of predictive performance indicated a strong agreement between tests.ConclusionsSynovial fluid IL-6 is not superior to synovial fluid WBC count and %PMN in detecting PJI.Level of Evidence: Therapeutic Level IICite this article: Bone Jt Open 2020;1-12:737–742.

Improved diagnosis of chronic hip and knee prosthetic joint infection using combined serum and synovial IL-6 tests.

AimsThis study aimed to explore whether serum combined with synovial interleukin-6 (IL-6) measurement can improve the accuracy of prosthetic joint infection (PJI) diagnosis, and to establish the cut-off values of IL-6 in serum and synovial fluid in detecting chronic PJI.MethodsPatients scheduled to have a revision surgery for indications of chronic infection of knee and hip arthroplasties or aseptic loosening of an implant were prospectively screened before being enrolled into this study. The Musculoskeletal Infection Society (MSIS) definition of PJI was used for the classification of cases as aseptic or infected. Serum CRP, ESR, IL-6, and percentage of polymorphonuclear neutrophils (PMN%) and IL-6 in synovial fluid were analyzed. Statistical tests were performed to compare these biomarkers in the two groups, and receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker.ResultsA total of 93 patients were enrolled. There was no difference in demographic data between both groups. Synovial fluid IL-6, with a threshold of 1,855.36 pg/ml, demonstrated a mean sensitivity of 94.59% (95% confidence interval (CI) 81.8% to 99.3%) and a mean specificity of 92.86% (95% CI 82.7 to 98.0) for detecting chronic PJI. Then 6.7 pg/ml was determined to be the optimal threshold value of serum IL-6 for the diagnosis of chronic PJI, with a mean sensitivity of 97.30% (95% CI 85.8% to 99.9%) and a mean specificity of 76.79% (95% CI 63.6% to 87.0%). The combination of synovial IL-6 and serum IL-6 led to improved accuracy of 96.77% in diagnosing chronic PJI.ConclusionThe present study identified that a combination of IL-6 in serum and synovial IL-6 has the potential for further improvement of the diagnosis of PJI.Cite this article: Bone Joint Res 2020;9(9):587–592.

Low-Intensity Pulsed Ultrasound Alleviates Osteoarthritis Condition Through Focal Adhesion Kinase-Mediated Chondrocyte Proliferation and Differentiation.

Osteoarthritis (OA) is a prevalent chronic multifactorial degenerative disease characterized by joint tissue inflammation, osteophyte formation, subchondral bone sclerosis, and articular cartilage degradation. Low-intensity pulsed ultrasound (LIPUS), a noninvasive ultrasound technique, is widely used to attenuate diseases. The aim of this study was to investigate whether LIPUS can ameliorate OA, and to explore its underlying molecular mechanism. The OA model was established in a C57BL/6 mouse by the anterior cruciate ligament transaction method. OA was assessed using arthritis scoring and weightbearing parameters. Chondrocyte proliferation was detected by a CCK-8 assay. The levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) in synovial fluid of the mice were measured by enzyme-linked immunosorbent assay. In OA mice, the arthritis score and weightbearing abilities were dramatically improved by LIPUS treatment. LIPUS also remarkably declined the levels of inflammatory cytokines IL-6, IL-8, and TNF-α in synovial fluid of OA mice. Moreover, LIPUS promoted chondrocyte proliferation and differentiation by activating focal adhesion kinase (FAK) signaling. Inhibition of FAK significantly blocked LIPUS-mediated cell proliferation and differentiation in vitro, as well as inflammation condition in OA mice. LIPUS alleviates OA through promoting chondrocytes proliferation and differentiation by activating FAK, which could act as an intervening target for OA treatment.

Elevated plasma and synovial fluid interleukin-8 and interleukin-18 may be associated with the pathogenesis of knee osteoarthritis

PurposeOsteoarthritis (OA) of the knee is a multifactorial degenerative disease typically defined as the ‘wear and tear’ of articular joint cartilage. However, recent studies suggest that OA is a disease arising from chronic low-grade inflammation. We conducted a study to investigate the relationship between chronic inflammatory mediators present in both the systemic peripheral blood system and localised inflammation in synovial fluid (SF) of OA and non-OA knees; and subsequently made direct comparative analyses to understand the mechanisms that may underpin the processes involved in OA. Methods20-Plex proteins were quantified using Human Magnetic Luminex® assay (R&D Systems, USA) from plasma and SF of OA (n = 14) and non-OA (n = 14) patients. Ingenuity Pathway Analysis (IPA) software was used to predict the relationship and possible interaction of molecules pertaining to OA. ResultsThere were significant differences in plasma level for matrix metalloproteinase (MMP)-3, interleukin (IL)-27, IL-8, IL-4, tumour necrosis factor-alpha, MMP-1, IL-15, IL-21, IL-10, and IL-1 beta between the groups, as well as significant differences in SF level for IL-15, IL-8, vascular endothelial growth factor (VEGF), MMP-1, and IL-18. Our predictive OA model demonstrated that toll-like receptor (TLR) 2, macrophage migration inhibitory factor (MIF), TLR4 and IL-1 were the main regulators of IL-1B, IL-4, IL-8, IL-10, IL-15, IL-21, IL-27, MMP-1 and MMP-3 in the plasma system; whilst IL-1B, TLR4, IL-1, and basigin (BSG) were the regulators of IL-4, IL-8, IL-10, IL-15, IL-18, IL-21, IL-27, MMP-1, and MMP-3 in the SF system. ConclusionThe elevated plasma IL-8 and SF IL-18 may be associated with the pathogenesis of OA via the activation of MMP-3.