Cytokines In Synovial Fluid Research Articles

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The objective of the study was to evaluate cytokine concentration and profile of lipid peroxidation in synovial fluid of patients with osteoarthritis and concomitant defects of articular surfaces. Material and methods Synovial fluid samples were taken from 102 patients with osteoarthritis of the knee joint. Patients with rheumatoid arthritis, osteoarthritis of a post-traumatic etiology, and somatic diseases that could affect results of the study were excluded from the study. Thirty control samples originated from deceased donors of both genders. Synovial fluid was extracted in compliance with Ministry of Health Order No. 694 dtd July 21, 1978, p. 2.24 Guidelines of forensic medical examination in the USSR. Results Findings of laboratory studies showed statistically significant differences in synovial fluid cytokine levels depending on absence or presence of defects on the tibial condyles. Biochemical tests revealed greater changes in lipid peroxidation in patients with articular defects. Total level of lipid peroxidation products resulting in the formation of conjugated dienes (CD), malondialdehyde (MDA) was shown to increase in both groups of patients being significantly higher in patients with defects on articular surfaces. Primary (conjugated dienes) and secondary (malondialdehyde) lipid peroxidation products accumulated in the synovial fluid of the patients with the levels being significantly increased in both groups with no changes in the CD/MDA ratio. Patients with defects on articular surfaces demonstrated increased formation of primary products, and non-defect group showed greater formation of secondary products. Antioxidant enzyme, catalase, appeared to me more active in patients of Group I. Conclusion The findings can be used to evaluate defects on articular surface and identify strategies of medication therapy.

Cartilage repair in degenerative osteoarthritis mediated by squid type II collagen via immunomodulating activation of M2 macrophages, inhibiting apoptosis and hypertrophy of chondrocytes

Cartilage lesions in degenerative osteoarthritis (OA) are involved with pathological microenvironmental alterations induced by inflammatory macrophages, and apoptotic and/or hypertrophic chondrocytes. However, current non-operative therapies for cartilage repair in OA can rarely achieve long-term and satisfactory outcomes. This study aims to evaluate a newly developed squid type II collagen (SCII) for repairing OA-induced cartilage lesions. Our in vitro data show that SCII induces M2 polarization of macrophages, and activates macrophages to express pro-chondrogenic genes (TGF-β and IGF), which greatly improves the microenvironment around chondrocytes to produce type II collagen and glycosaminoglycan. In addition, glycine in SCII activates glycine receptors on inflammatory chondrocytes to decrease intracellular calcium concentration, leading to effective inhibition of chondrocyte apoptosis and hypertrophy. The in vitro effects of SCII are further confirmed in vivo. In a rat model of OA, SCII increases the ratio of M2 macrophages, elevates the levels of pro-chondrogenic cytokines (TGF-β1 and TGF-β3) in synovial fluid, and inhibits chondrocyte apoptosis and MMP13 production. Our findings show that SCII immunomodulates M2 activation of macrophages to skew the local OA microenvironment towards a pro-chondrogenic atmosphere, and promotes cartilage repair under inflammatory condition. It shows great potential for SCII to be a novel biomaterial for cartilage repair in OA.

Synovial Fluid Cytokine Concentrations Are Influenced by Disease Etiology

Synovial Fluid Cytokine Concentrations Are Influenced by Disease Etiology

The Use of Synovial Fluid Analysis for Diagnosis of Temporomandibular Joint Disorders.

There has been considerable progress in the identification of the various synovial fluid cytokines and growth factors associated with various disorders of the temporomandibular joint. However, the presence of the same inflammatory mediators and proteins in these conditions, despite differing causes, makes it very difficult to identify the specific disease using synovial fluid analysis alone.

Functional folate receptor cell-associated inflammatory cytokines predict the progression of knee osteoarthritis

Purpose: In our prior study using 99mTc-EC20 (Etarfolatide) imaging, we observed folate receptor positive (FR+) cells in vivo in the synovium of the majority (76%) of knees of patients with osteoarthritis (OA). The quantity of these FR+ cells was associated with radiographic severity of knee joint space narrowing and osteophyte and knee pain. To identify the cells with functional folate receptors and their involvement in disease pathogenesis and progression in knee OA, we characterized the immune cell populations of OA synovium and synovial fluid by flow cytometry and evaluated the correlation of functional folate receptor positive phenotypes with cytokine production, knee OA severity and progression. Based on results from our pilot Etarfolatide study, we hypothesized that immune cells bearing functional folate receptors would be pro-inflammatory. Methods: For these analyses, we evaluated specimens from three different cohorts. Total Knee Replacement (TKR) Cohort: waste synovial tissue (SV) and matched synovial fluid (SF) obtained from knee OA patients at the time of total knee arthroplasty (n=18) at Duke University Hospital. Cell populations from SV and SF were phenotyped for cell surface markers and functional FR (FR+ detected by incubating cells with fluorescently labeled folate conjugate) using polychromatic flow cytometry. The EC20 Scan Cohort: SF from radiographic knee OA patients (Kellgren-Lawrence (KL) grade 1-4) (n=26 knees), Etarfolatide and computed tomography (CT) imaging. The Prediction of Osteoarthritis Progression (POP) Cohort: SF samples from radiographic knee OA patients (KL grade 1-3) with three-year follow-up and available SF (n=107 knees). Inflammatory cytokines were quantified in SF from all three cohorts and concentrations correlated with the immunophenotypic and imaging data. Results: Using polychromatic flow cytometry, FR+ macrophages and neutrophils were identified in both the SF and SV of the TKR cohort (Table 1). On a per cell basis, neutrophils took up significantly more folate conjugate than macrophages. Among the SF cytokines, transforming growth factor beta 1 (TGF-β1) and neutrophil elastase correlated with FR+ macrophages and FR+ neutrophils, respectively. The SF concentration of both of these cytokines were strongly correlated with the in vivo FR+ synovial phenotype by Etarfolatide uptake in the EC20 cohort (p < 0.0001). TGF-β1 and elastase were both strongly correlated with the osteophyte (OST) score (p < 0.05) in the EC20 (evaluated by CT) and POP (evaluated by radiograph) cohorts. Lastly, in the POP cohort, baseline TGF-β1 and elastase were associated with knee OA progression based on disease outcomes (no progression, radiographic features of OST, OST plus joint space narrowing (JSN) and total knee replacement (TKR) in sequence for linear trend analysis) (p<0.0001 and p=0.0014, respectively) (Fig 1A). Receiver operating characteristics (ROC) analysis of SF TGF-β1 (adjusting for age, BMI, gender, baseline OST and JSN) for the determination of any knee OA progression (either OST, JSN or TKR progression vs. non-progression) yielded an area under the curve (AUC) of 0.95 (95% CI [0.87, 0.98]) (Fig 1B). ROC analysis of elastase yielded an AUC of 0.90 (CI [0.80, 0.95]) (Fig 1B). Applying the Youden index as the cut-off value, for TGF-β1 the sensitivity was 97% (CI [89, 99]), the specificity 85% (CI [62, 97]), and the positive predictive value (PPV) 95% (CI [88, 98]). For elastase the sensitivity was 85% (CI [74, 0.92]), the specificity 86% (CI [65, 97]), and the PPV 95% (CI [86, 98]). Conclusions: We have identified activated macrophages and neutrophils as the functional folate receptor bearing cells in knee OA. The correlation of SF TGF-β1 and elastase with the EC20 imaging phenotype confirmed the pro-inflammatory nature of the FR+ cells in vivo. We further confirmed the pro-inflammatory nature of these cells based on the association of these cell markers with knee OA progression. Taken together, these results suggest that these cells could be potential therapeutic targets in OA. The promising AUC scores for these markers also suggest that SF TGF-β1 and elastase could be the novel biomarkers of risk of progression in knee OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Pattern of synovial fluid cytokine biomarkers in the knee after anterior cruciate ligament tear suggests an initial repair response

Pattern of synovial fluid cytokine biomarkers in the knee after anterior cruciate ligament tear suggests an initial repair response

Paper #19 - Analysis of Synovial Fluid Cytokine Profiles in Determining Significance of Positive Culture Results in Patients Undergoing Primary Total Shoulder Arthroplasty for Glenohumeral Osteoarthritis

Introduction: Determining the significance of a positive culture result in revision shoulder arthroplasty can be challenging, due to the indolent nature of the commonly cultured organisms, most notably P. acnes. Recent studies have also shown a significant positive culture rate with P. acnes following primary shoulder arthroplasty in patients with no prior history of shoulder surgery. These findings suggest that some P. acnes culture growth following shoulder arthroplasty may represent culture contaminant or non-infectious colonization, rather than true infection. However, further data is needed to clarify such distinctions. We have previously demonstrated the benefit of synovial fluid cytokine analysis in the diagnosis of shoulder periprosthetic joint infection (PJI). The purpose of this study was to compare synovial fluid cytokine profiles and culture results in patients with primary glenohumeral osteoarthritis (OA) undergoing primary total shoulder arthroplasty (TSA) to non-arthritic patients undergoing primary arthroscopic rotator cuff repair (RCR), in order to determine if cytokine levels can distinguish the significance of a positive culture result.

Serum and synovial fluid cytokine profiling in hip osteoarthritis: distinct from knee osteoarthritis and correlated with pain

BackgroundInflammation is associated with the onset and progression of osteoarthritis in multiple joints. It is well known that mechanical properties differ between different joints, however, it remains unknown if the inflammatory process is similar/distinct in patients with hip vs. knee OA. Without complete understanding of the role of any specific cytokine in the inflammatory process, understanding the ‘profile’ of inflammation in a given patient population is an essential starting point. The aim of this study was to identify serum cytokine profiles in hip Osteoarthritis (OA), and investigate the association between cytokine concentrations and clinical measurements within this patient population and compare these findings to knee OA and healthy control cohorts.MethodsIn total, 250 serum samples (100 knee OA, 50 hip OA and 100 control) and 37 synovial fluid samples (8 knee OA, 14 hip OA and 15 control) were analyzed using a multiplex ELISA based approach. Synovial biopsies were also obtained and examined for specific cytokines. Pain, physical function and activity within the hip OA cohort were examined using the HOOS, SF-36, HHS and UCLA outcome measures.ResultsThe three cohorts showed distinct serum cytokine profiles. EGF, FGF2, MCP3, MIP1α, and IL8 were differentially expressed between hip and knee OA cohorts; while FGF2, GRO, IL8, MCP1, and VEGF were differentially expressed between hip OA and control cohorts. Eotaxin, GRO, MCP1, MIP1β, VEGF were differentially expressed between knee OA and control cohorts. EGF, IL8, MCP1, MIP1β were differentially expressed in synovial fluid from a sub-set of patients from each cohort. Specifically within the hip OA cohort, IL-6, MDC and IP10 were associated with pain and were also found to be present in synovial fluid and synovial membrane (except IL-6) of patients with hip OA.ConclusionOA may include different inflammatory subtypes according to affected joints and distinct inflammatory processes may drive OA in these joints. IL6, MDC and IP10 are associated with hip OA pain and these proteins may be able to provide additional information regarding pain in hip OA patients.

Conditional Macrophage Depletion Increases Inflammation and Does Not Inhibit the Development of Osteoarthritis in Obese Macrophage Fas-Induced Apoptosis-Transgenic Mice.

To investigate whether short-term, systemic depletion of macrophages can mitigate osteoarthritis (OA) following injury in the setting of obesity. CSF-1R-GFP+ macrophage Fas-induced apoptosis (MaFIA)-transgenic mice that allow conditional depletion of macrophages were placed on a high-fat diet and underwent surgery to induce knee OA. A small molecule (AP20187) was administrated to deplete macrophages in MaFIA mice. The effects of macrophage depletion on acute joint inflammation, OA severity, and arthritic bone changes were evaluated using histology and micro-computed tomography. Immunohistochemical analysis was performed to identify various immune cells. The levels of serum and synovial fluid cytokines were also measured. Macrophage-depleted mice had significantly fewer M1 and M2 macrophages in the surgically operated joints relative to controls and exhibited decreased osteophyte formation immediately following depletion. Surprisingly, macrophage depletion did not attenuate the severity of OA in obese mice; instead, it induced systemic inflammation and led to a massive infiltration of CD3+ T cells and particularly neutrophils, but not B cells, into the injured joints. Macrophage-depleted mice also demonstrated a markedly increased number of proinflammatory cytokines including granulocyte colony-stimulating factor, interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor in both serum and joint synovial fluid, although the mice showed a trend toward decreased levels of insulin and leptin in serum after macrophage depletion. Our findings indicate that macrophages are vital for modulating homeostasis of immune cells in the setting of obesity and suggest that more targeted approaches of depleting specific macrophage subtypes may be necessary to mitigate inflammation and OA in the setting of obesity.

CD56+/CD16- Natural Killer cells expressing the inflammatory protease granzyme A are enriched in synovial fluid from patients with osteoarthritis.

Natural killer (NK) cells have been involved in the pathology of different inflammatory and autoimmune disorders. Inflammation is an important regulator of osteoarthritis (OA), but the molecular and cellular mechanisms regulating this process are not well defined. To understand the role of NK cells in OA, we have compared the phenotype (CD56 subsets and perforin and granzyme expression) and cytotoxic function of NK cells in peripheral blood and synovial fluid from patients with OA undergoing total knee arthroplasty. In contrast to peripheral blood lymphocytes (PBLs), the majority of NK cells from the synovial fluid were CD56brightCD16(-) cells. As expected the expression of the cytolytic mediators perforin and granzyme B in CD56brightCD16(-) cells was low and correlated with a poor cytotoxic potential against K562 sensitive target cells. Surprisingly, this low cytotoxic NK cell subset expressed high levels of granzyme A (a protease recently characterized as a key modulator of inflammation in mouse models) in synovial fluid but not in peripheral blood. The presence of the CD56(+)brightCD16(-) cells expressing granzyme A correlated with increased levels of pro-inflammatory cytokines in synovial fluid from OA patients. Our results indicate that NK cells from the synovium of patients with OA, which present an immunoregulatory non-cytotoxic phenotype, show different phenotype comparing with NK cells from peripheral blood, especially expressing granzyme A, a pro-inflammatory molecule which may contribute to the establishment of chronic articular inflammation in this type of patients.

Correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary total knee arthroplasty

BackgroundDespite the success of total knee arthroplasty (TKA) in reducing knee pain and improving functional disability, the management of acute postoperative pain is still unsatisfactory. This study was aimed to quantitatively analyze the possible correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary TKA.MethodsPatients scheduled for unilateral primary TKA were consecutively included, the serial changes of the numerical rating scale (NRS) at rest (NRSR) and at walking (NRSW), serum inflammatory cytokines and muscle damage markers were assessed before surgery (T0) and at postoperative day 1, 2, 3 and 5 (T1-T4, respectively); while pain disability questionnaire (PDQ) and synovial fluid inflammatory cytokines were evaluated at T0. The correlations between inflammatory cytokines, muscle damage markers and pain scores were examined, and Bonferroni correction was applied for multiple comparisons.ResultsNinety six patients were included for serum markers and pain evaluations at T0-T4, while 54 (56.25%) for synovial fluid cytokines at T0. The NRSR at T1 and T2 were positively correlated with preoperative NRSW, while the NRSW at T1 to T4 were positively correlated with preoperative NRSR, NRSW and PDQ (all p < 0.05). The NRSR was positively correlated with serum PGE2, IL-6, and CK at T1; the NRSW was positively correlated with serum CRP at T1, with PGE2 and IL-6 at T1 to T3, with CK at T2 and T4, and with Mb and LDH at T1 to T4 (all p < 0.003). Meanwhile, positive correlations were observed between preoperative NRSW and synovial fluid PGE2, IL-6, IL-8, or TNF-α, as well as between PDQ and PGE2 (all p < 0.003), but no associations between postoperative pain scores and preoperative synovial fluid cytokines was found (all p ≥ 0.003). Additionally, the NRSR at T1 and T2, and NRSW at T1 to T4 were positively correlated with body mass index (all p < 0.05).ConclusionsSerum inflammatory cytokines and muscle damage markers are positively correlated with acute postoperative pain following primary TKA, and the key cytokines (CRP, PGE2, and IL-6) and markers (Mb, CK and LDH) may serve as the targets for developing novel analgesic strategies.

Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid: an exploratory analysis in the KANON trial.

Prospectively monitor how treatment of acutely ruptured anterior cruciate ligament (ACL) affects biomarkers of inflammation and proteolytic degradation over 5 years. We studied 119 subjects with acute ACL injury from the randomized controlled knee anterior cruciate ligament, non-surgical versus surgical treatment (KANON)-trial (Clinical trial ISRCTN 84752559) who had synovial fluid, serum and urine samples available from at least two out of six visits over 5 years after acute ACL rupture. All subjects followed a similar rehabilitation protocol where, according to randomization, 60 also had early ACL reconstruction and 59 had the option to undergo a delayed ACL reconstruction if needed. Interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), tumor necrosis factor (TNF), amino acids alanine, arginine, glycine, serine (ARGS)-aggrecan, C-terminal crosslinking telopeptide type II collagen (CTX-II) and N-terminal crosslinking telopeptide type I collagen (NTX-I) were quantified by enzyme-linked immunosorbent assays (ELISA). Subjects randomized to early ACL reconstruction had higher cytokine concentrations in index knee synovial fluid at 4 months (IL-6, IL-8, IL-10, TNF), 8 months (IL-6 and TNF) and at 5 years (IFNγ) compared to those randomized to optional delayed reconstruction. Those that underwent delayed ACL reconstruction within 5 years (30 subjects), had higher synovial fluid concentrations of IL-6 at 5 years compared to those treated with rehabilitation alone. No differences between groups were noted for ARGS-aggrecan in synovial fluid and serum or CTX-II and NTX-I in urine over 5 years, neither as randomized nor as treated. Surgical ACL reconstruction constitutes a second trauma to the acutely injured joint resulting in a prolonged elevation of already high synovial fluid levels of inflammatory cytokines.

Synovial fluid cytokine levels in diagnosis of indolent prosthetic shoulder joint infection

Periprosthetic joint infection is one of the most serious complications associated with arthroplasty surgery and poses great diagnostic difficulty. Traditional diagnostic methods used to diagnose infection in the lower extremity are less accurate for shoulder prosthetic joint infection due to the indolent nature of the most common pathogen, Propionibacterium acnes. In addition to preoperative lab work and intraoperative tissue cultures, a more recent tool for the evaluation of periprosthetic infection has been analysis of synovial fluid for antimicrobial peptides and cytokines. Investigation of synovial biomarkers such as α-defensin and interleukins offers improved ability to more accurately diagnose prosthetic shoulder joint infection.

Inflammation affects the viability and plasticity of equine mesenchymal stem cells: possible implications in intra-articular treatments.

Mesenchymal stem cells (MSCs) are gaining relevance for treating equine joint injuries because of their ability to limit inflammation and stimulate regeneration. Because inflammation activates MSC immunoregulatory function, proinflammatory priming could improve MSC efficacy. However, inflammatory molecules present in synovial fluid or added to the culture medium might have deleterious effects on MSCs. Therefore, this study was conducted to investigate the effects of inflammatory synovial fluid and proinflammatory cytokines priming on viability and plasticity of equine MSCs. Equine bone marrow derived MSCs (eBM-MSCs) from three animals were cultured for 72 h in media supplemented with: 20% inflammatory synovial fluid (SF); 50 ng/mL IFN-γ and TNF-α (CK50); and 20 ng/mL IFN-γ and TNF-α (CK20). Proliferation assay and expression of proliferation and apoptosis-related genes showed that SF exposed-eBM-MSCs maintained their viability, whereas the viability of CK primed-eBM-MSCs was significantly impaired. Tri-lineage differentiation assay revealed that exposure to inflammatory synovial fluid did not alter eBM-MSCs differentiation potential; however, eBM-MSCs primed with cytokines did not display osteogenic, adipogenic or chondrogenic phenotype. The inflammatory synovial environment is well tolerated by eBM-MSCs, whereas cytokine priming negatively affects the viability and differentiation abilities of eBM-MSCs, which might limit their in vivo efficacy.

Transient receptor potential canonical 5 (TRPC5) protects against pain and vascular inflammation in arthritis and joint inflammation

ObjectiveTransient receptor potential canonical 5 (TRPC5) is functionally expressed on a range of cells including fibroblast-like synoviocytes, which play an important role in arthritis. A role for TRPC5 in inflammation...

Differential gene and protein expression of chemokines and cytokines in synovial fluid of patients with arthritis.

BackgroundPsoriatic arthritis (PsA), an inflammatory musculoskeletal disease, develops in approximately 30% of patients with psoriasis. Previously, chemokine (C-X-C motif) ligand 10 (CXCL10) was identified as a predictive biomarker of PsA in patients with psoriasis and was reduced after development of PsA. The purpose of the present study was to explore messenger RNA (mRNA) and protein expression of CXCL10 and its receptor, chemokine (C-X-C motif) receptor 3 (CXCR3), in the joints of patients with PsA to gain insight into their role in the pathogenesis of the disease.MethodsSera from 47 patients with PsA and 33 healthy control subjects were compared for expression of CXCL10 by Luminex assay. Synovial fluid (SF) was obtained from patients with PsA (n = 40), osteoarthritis (OA; n = 14), gout (n = 8), and rheumatoid arthritis (RA; n = 11) during clinical care. SF mRNA and protein expression of CXCL10, interleukin-17A (IL-17A), CXCR3, TBX21, RORC and/or interferon γ (IFNγ) were compared among the above-mentioned disease groups, as well as in paired SF and serum samples from patients with PsA using real-time polymerase chain reaction and Luminex assays, respectively.ResultsSerum CXCL10 was significantly higher in patients with PsA than in control subjects (p = 0.0007). CXCL10, IL-17A, and TBX21 expression were elevated in SF cells of patients with PsA compared with those of patients with OA and gout, but not those of patients with RA. CXCR3 and RORC were elevated in PsA SF cells compared with all other patient groups. Concordant results were obtained for CXCL10 and IL-17A protein expression. IFNγ was elevated in PsA SF compared with OA SF (p = 0.015). CXCL10 protein expression was substantially increased in SF (median 7283.9 pg/ml, interquartile range [IQR] 1330–10,362 pg/ml) compared with paired serum samples (median 282.06, IQR 180.7–395.8 pg/ml; p = 0.001), whereas IFNγ was significantly reduced (SF median 6.03 pg/ml, IQR 4.47–8.94 pg/ml; versus serum median 23.70 pg/ml, IQR 3.2–104.6 pg/ml; p = 0.001).ConclusionsCXCL10 may have an important etiological role in PsA that is analogous to that in RA, and it is a candidate biomarker to distinguish PsA from healthy individuals and from patients with OA and gout.

Inflammatory cytokine levels in synovial fluid 3, 4days postoperatively and its correlation with early-phase functional recovery after anterior cruciate ligament reconstruction: a cohort study.

BackgroundSynovial fluid was collected prior to and at 3 to 4 days after ACL reconstruction to investigate the correlation between inflammatory cytokine levels in the acute phase after surgery and physical functional recovery at 3 months postoperatively.Methods For this purpose, 79 patients with ACL reconstruction using semitendinosus tendons were included in the study. Median days from injury to surgery were 80 days (13–291 days). Synovial fluid was obtained just before surgery and at 3 to 4 days after surgery. Physical activity of each patient was evaluated at 3 months postoperatively, and scored from 0 (hard to walk) to 5 (run). Patients able to jog (score 4) or run (score 5) were considered as the “quick recovery” group and others (scores 1–3) as the “delayed recovery” group.ResultsPhysical activity recovery scores in the early surgery group (preoperative period less than 60 days; Group I) were significantly better than those in the delayed surgery group (Group II). Among the cytokines tested, TNF-alpha and IL10 levels in synovial fluid were significantly higher in Group II at 3 to 4 days postoperatively, while levels of these cytokines were quite comparable preoperatively between the groups. Increased IL1-beta expression was noted in the delayed recovery group at 3 to 4 days postoperatively. In addition, levels of IL6, IL10 and IFN-gamma also tended to increase in patients with delayed recovery.ConclusionDelayed ACL reconstruction increases levels of inflammatory cytokines in synovial fluid after surgery and correlates with a prolonged recovery of short-period physical activity of the patients.

Neer Award 2015: Analysis of cytokine profiles in the diagnosis of periprosthetic joint infections of the shoulder

Periprosthetic joint infection (PJI) after shoulder arthroplasty can present a diagnostic and therapeutic challenge. This study evaluated the diagnostic utility of broader synovial fluid cytokine analysis for identifying PJI in patients undergoing revision shoulder arthroplasty. Synovial fluid levels of 9 cytokines (interleukin [IL] 6, granulocyte-macrophage colony-stimulating factor, IL-1β, IL-12, IL-2, IL-8, interferon-γ, IL-10, and tumor necrosis factor-α) were measured in 75 cases of revision shoulder arthroplasty with a multiplex immunoassay. Cases were classified into infection categories and groups based on objective perioperative findings. Differences in cytokine levels among infection groups were evaluated. Receiver operating characteristic curves were used to assess the diagnostic utility of the individual synovial fluid cytokines and combinations of cytokines in determining infection status. Synovial IL-6, granulocyte-macrophage colony-stimulating factor, interferon-γ, IL-1β, IL-2, IL-8, and IL-10 were significantly elevated in cases of revision shoulder arthroplasty classified as infected. Individually, IL-6, IL-1β, IL-8, and IL-10 showed the best combination of sensitivity and specificity for predicting infection, and a combined cytokine model consisting of IL-6, tumor necrosis factor-α, and IL-2 showed better diagnostic test characteristics than any cytokine alone, with sensitivity of 0.80, specificity of 0.93,, positive and negative predictive values of 0.87 and 0.89, and positive and negative likelihood ratios of 12.0 and 0.21. Individual and combined synovial fluid cytokine analysis were both more effective than routine perioperative testing, such as serum erythrocyte sedimentation rate and C-reactive protein, in the diagnosis of PJI of the shoulder. Once validated, combined synovial fluid cytokine analysis could be used as a predictive tool to determine the probability of PJI in patients undergoing revision shoulder arthroplasty and better guide treatment.

Running decreases knee intra-articular cytokine and cartilage oligomeric matrix concentrations: a pilot study.

Regular exercise protects against degenerative joint disorders, yet the mechanisms that underlie these benefits are poorly understood. Chronic, low-grade inflammation is widely implicated in the onset and progression of degenerative joint disease. To examine the effect of running on knee intra-articular and circulating markers of inflammation and cartilage turnover in healthy men and women. Six recreational runners completed a running (30min) and control (unloaded for 30min) session in a counterbalanced order. Synovial fluid (SF) and serum samples were taken before and after each session. Cytokine concentration was measured in SF and serum using a multiplexed cytokine magnetic bead array. Ground reaction forces were measured during the run. There were no changes in serum or SF cytokine concentration in the control condition. The cytokine GM-CSF decreased from 10.7±9.8 to 6.2±5.9pg/ml pre- to post-run (p=0.03). IL-15 showed a trend for decreasing concentration pre- (6.7±7.5pg/ml) to post-run (4.3±2.7pg/ml) (p=0.06). Changes in IL-15 concentration negatively correlated with the mean number of foot strikes during the run (r 2=0.67; p=0.047). The control condition induced a decrease in serum COMP and an increase in SF COMP, while conversely the run induced an increase in serum COMP and a decrease in SF COMP. Changes in serum and SF COMP pre- to post-intervention were inversely correlated (r 2=0.47; p=0.01). Running appears to decrease knee intra-articular pro-inflammatory cytokine concentration and facilitates the movement of COMP from the joint space to the serum.

Gene polymorphism and levels of pro-inflammatory cytokines in plasma and synovial fluid of patients with posttraumatic knee osteoarthritis

Posttraumatic knee osteoarthritis patients (n = 117) and healthy individuals (n = 94) were investigated to determine the genotype and allelic frequency distribution of polymorphic loci Т-31С, С + 3953Т IL-1β and G-308A TNF-α. The plasma and synovial fluid levels of proinflammatory cytokines IL-1β and TNF-α were also measured in 31 patients. The study demonstrated that the plasma and synovial fluid levels of IL-1β but not TNF-α were increased in patients with posttraumatic knee osteoarthritis. Also, the linkage between TNF-α levels and polymorphic locus G-308A TNF-α was shown: the presence of allele–308А was associated with decreased TNF-α levels. It was found that polymorphic loci Т-31С, С+3953Т IL-1β, and G-308A TNF-α are not markers of predisposition to posttraumatic knee osteoarthritis in Russian population of Rostov Oblast.