TNF-α In Synovial Fluid Research Articles

Intra-articular injection of chitosan combined with low-dose glucocorticoid for the treatment of knee osteoarthritis in early and middle stages.

This study explores the clinical efficacy of intra-articular injection of chitosan combined with low-dose glucocorticoid for the treatment of knee osteoarthritis in early and middle stages. The visual analog scale (VAS) score, Lysholm score, Hospital for Special Surgery (HSS) score, and changes in the levels of inflammatory cytokines IL-1, IL-6, and TNF-α in the joint fluid before and after treatment in the 3 groups were compared, and the clinical efficacy was evaluated. All cases were followed up, with a follow-up time of 7 to 12 months, and no lost cases. The horizontal comparison showed that the VAS score, Lysholm score, HSS score, and levels of inflammatory cytokines IL-1, IL-6, and TNF-α in the joint fluid after treatment in each group were better than before treatment, and the difference was statistically significant (P < .05). The longitudinal comparison showed that there was no significant difference in VAS score, Lysholm score, HSS score and levels of inflammatory cytokines IL-1, IL-6, and TNF-α in synovial fluid among the 3 groups before treatment (P > .05); However, after treatment, there were significant differences among the 3 groups (P < .05), group C was better than group A and group B, group B was better than group A, and the differences were statistically significant (P < .05). The difference in clinical efficacy among the 3 groups was statistically significant (P < .05). The clinical efficacy of chitosan combined with low-dose glucocorticoid intra-articular injection in the treatment of knee osteoarthritis in early and middle stages is significant, with the characteristics of small trauma, rapid onset, and lasting efficacy, and it avoids the adverse reactions of topical or oral nonsteroidal anti-inflammatory drugs. As a first-line treatment option, it is recommended for promotion and use in clinical practice.

Correlation Between Synovial Fluid Levels of Matrix Metalloproteinase's (MMP-1, MMP-3, and MMP-9) and TNF-α with the Severity of Osteoarthritis Knee in Rural Indian Population.

In India, 22% to 39% of the ageing population suffers from degenerative knee osteoarthritis (OA), making it the most prevalent joint disorder in the knee. MMP-1, MMP-3, and MMP-9 protein expression levels have all been associated with OA. The aim of the present study was to establish a relationship between synovial fluid levels of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9), and tumour necrosis factor-alpha (TNF-α) with different Kellgren-Lawrence Grading scale as per the severity of knee osteoarthritis (OA). This hospital-based observational study included 87 individuals with knee osteoarthritis examined at the orthopaedics department outpatient clinic at the tertiary care teaching hospital in rural area of north India. In-person interviews were conducted to gather data, through a semi-structured, pretested interview schedule. To determine the degree and severity of OA, the levels of the enzymes matrix metalloproteinase MMP-1, MMP-3, and MMP-9 as well as tumour necrosis factor (TNF-α) were assessed in the synovial fluid of knee of each study participant. The levels of MMP-1, MMP-3, MMP-9, and TNF-α in synovial fluid were significantly correlated with the severity of osteoarthritis as determined by the Kellgren-Lawrence Grading Scale. Age, duration of symptoms and BMI showed a strong positive and significant correlation with biochemical markers (MMP-1, MMP-3, MMP-9, and TNF-α) in synovial fluid of Knee. Level of biochemical markers (MMP-1, -3, -9, and TNF-α) in synovial fluid act as diagnostic markers and have a positive correlation with the severity of osteoarthritis knee, age, weight/BMI and duration of disease. However, no significant correlation was found between the level of aforementioned biochemical markers with sex, height, inflammation of the knee, morning stiffness, and age of onset of disease.

TME disk deplasmanında synovial sıvı pro-inflamatuar sitokinlerin ve klinik bulguların değerlendirilmesi

Aims: Temporomandibular disorders (TMD) are common musculoskeletal disease that affects the soft tissues and bone structures of the temporomandibular joint (TMJ). Inflammatory mediators play a critical role in the etiology of TMD by affecting various molecular mechanisms. This study aims to investigate the effect of pro-inflammatory cytokines on TMJ internal derangements and evaluate the relationship between clinical features.&#x0D; Methods: Patients who underwent arthrocentesis because of TMD were included in this study. Patients were divided into 2 groups according to anterior disc displacement with reduction (Group 1) and without reduction ( Group 2). Clinical findings before and after the arthrocentesis were evaluated retrospectively. Synovial fluid TNF-α, IL-1β, and IL-6 levels were analyzed with the ELISA method. &#x0D; Results: A total of 28 patients were included, with 15 patients in Group 1 and 13 patients in Group 2. All patients were female with an average age of 30.75±14.9. The average pre-operative pain score was 6.6±1.95 in all patients. After the arthrocentesis, the average pain score was 2.0 ( 1.0 - 2.5) and the difference was significant (p

Epigenetic modifications of tumor necrosis factor-alpha in joint cartilage tissue from osteoarthritis patients - CONSORT.

Background:Osteoarthritis (OA) remains one of the most common osteopathy for centuries, which can be attributed to multiple risk factors including mechanical and biochemical ones. More and more studies verified that inflammatory cytokines play important roles in the progression of OA, such as tumor necrosis factor-alpha (TNF-α). In this study, we aimed to investigate the relationship between epigenetic manifestations of TNF-? and the pathogenesis of OA.Methods:Totally, 37 OA patients’ cartilage was collected through the knee joint and 13 samples of articular cartilage as healthy control was collected through traumatic amputation. Real-time PCR, Western blot and ELISA analysis were performed to observe the expression of target genes and proteins in collected samples.Results:Compared with the healthy control group, TNF-? was over-expressing in cartilage which was collected from OA patients. DNA hypomethylation, histone hyperacetylation and histone methylation were observed in the TNF-? promoter in OA compared with normal patients, and we also studied series of enzymes associated with epigenetics. The results showed that by increasing DNA methylation and decreasing histone acetylation in the TNF-? promoter, and TNF-? over-expression in OA cartilage was suppressed, histone methylation has no significant correlation with OA.Conclusion:In conclusion, the changes of epigenetic status regulate TNF-α expression in the cells, which are pivotal to the OA disease process. These results may give us a better understanding of OA and may provide new therapeutic options.

Systemic and Local Cytokines Profile Determine Severity and Prognosis in Human Septic Arthritis

Septic arthritis (SA) is a medical emergency. The most common etiological agents are bacteria, which activate the local immune response coordinated by cytokines; however, little is known about the cytokine profile in human SA. To determine the association of local and systemic cytokine profiles with the severity and prognosis of patients with SA. Patients with clinical and laboratory diagnosed SA were enrolled as well as a control group. Serum and synovial fluid (SF) samples were obtained for determining cytokines and glucose levels; SF samples were used for histological analysis. Osteochondral damage and general health status and quality of life (SF-36) were evaluated during recruitment day. WOMAC osteoarthritis index score and SF-36 questionnaire were used a year after recruitment day as a follow up. A systemic and local proinflammatory cytokine profile was found in patients compared to the control group (p <0.05). IL-6 was 28 and 525 times higher than controls in sera and SF, respectively (p <0.0001). Systemic IL-6 correlated negatively with general mental health score (p=0.0184) and was associated with a higher osteoarthritis index after one year follow-up in the patients (p=0.0352). HMGB1 in SF was found higher in patients with SA (p <0.0001), and it was associated with osteochondral damage (p=0.0042). TNF-α in SF correlated negatively with SF-36 questionnaire one year after patients' recruitment in role limitation score (p=0.0318), body pain score (p=0.0315), and general mental health score (p=0.0197). Serum and SF cytokine signatures are associated with disease severity and prognosis in patients with SA.

Total Saponin of Dioscorea collettii Attenuates MSU Crystal-Induced Inflammation by Inhibiting the Activation of the TLR4/NF-κB Signaling Pathway.

Background Rhizomes from Dioscorea collettii are extensively used in traditional medicine for the treatment of arthritic diseases, particularly gouty arthritis (GA). This study aims to investigate whether the total saponin of Dioscorea collettii (TSD) can attenuate monosodium urate (MSU) crystal-induced inflammatory effects by suppressing the activation of the TLR4/NF-κB signaling pathway in vivo and in vitro. Methods Seventy-two male Wistar rats and THP-1 cells were used in this study. Pathological examination was used to examine the ankle joints of rats. The expression levels of TLR4, NF-κB, MyD88, and IL-1β were detected by qRT-PCR, Western blotting, or immunofluorescence. Results Compared with those in the normal group, the ankle joints of rats in the model group exhibited significant swelling, synovial tissue hyperplasia, inflammatory cell infiltration, and increased expression of IL-1β protein. The joint swelling degree of rats in the TSD high- and medium-dose groups and the colchicine group was significantly decreased, and the histopathology was obviously improved. TSD and colchicine reduced the levels of IL-1β and TNF-α in synovial fluid. They also decreased the mRNA expression of TLR4, NF-κB, and IL-1β in rat joint synovial tissue and the protein expression of TLR4, MyD88, and NF-κB. NF-κB protein expression in both the cytoplasm and nuclei of THP-1 cells showed the opposite trend. Furthermore, immunofluorescence showed that TSD reduced the nuclear translocation of NF-κBp65 in the model group. Conclusion TSD exhibits an anti-inflammatory effect in the MSU-induced inflammation model, and the mechanism may be to reduce the production of cytokines by inhibiting the activation of the TLR4/NF-κB signaling pathway.

Diagnostic Accuracy of Synovial Neopterin, TNF-α and Presepsin in Periprosthetic Joint Infection: A Prospective Study.

Due to the lack of specificity of conventional diagnostic tools, the prediction of periprosthetic joint infections (PJI) remains challenging. The purpose of this study was to evaluate the accuracy of synovial fluid neopterin, presepsin, and TNF-α as diagnostic parameters and to compare it to the biomarkers recommended in the 2018 definition of periprosthetic hip and knee infection. Between August 2018 and July 2019, a prospective cohort study was conducted in 80 patients with painful hip, shoulder, and knee arthroplasty. In addition to medical history, clinical and laboratory data were gathered. PJI was diagnosed based on the 2018 definition of periprosthetic hip and knee infection. Synovial joint fluid was analyzed for biomarker measurement using standard quantitative enzyme immunoassay kits. Fifty-three patients (66%) were classified as the aseptic group and twenty-seven patients (34%) as the PJI group. The mean levels of synovial fluid neopterin were significantly higher (p < 0.01) in the PJI group than those in the aseptic group (aseptic 8.3 ± 6.9 vs. PJI 20.9 ± 21.4 nmol/L). The average values of synovial fluid TNF-α and presepsin were not significantly higher in the PJI group than those in the aseptic group (presepsin: aseptic 0.13 ± 0.19 vs. PJI 0.11 ± 0.32 ng/mL, p = 0.08; TNF-α: aseptic 6.6 ± 7.3 vs. PJI 46.3 ± 123.2 pg/mL, p = 0.17). Synovial fluid neopterin was 59% specific and 74% sensitive with a cut-off value of 7.2 nmol/L. The sensitivity and specificity of synovial fluid TNF-α were 63 and 51% with a cut-off value of 3.9 pg/mL. Synovial fluid presepsin was 51% specific and 29% sensitive with a cut-off value above 0.06 ng/mL. Synovial fluid neopterin appears to a reliable diagnostic marker for detection of PJI. In contrast, synovial fluid TNF-α and presepsin are not suitable to exclude or diagnose PJI.

Synovial Mesenchymal Stem Cell-Derived EV-Packaged miR-31 Downregulates Histone Demethylase KDM2A to Prevent Knee Osteoarthritis

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have emerged as important mediators of intercellular communication in response to cartilage damage. In this study, we sought to characterize the inhibitory role of microRNA (miR)-31 encapsulated in synovial MSC (SMSC)-derived EVs in knee osteoarthritis (OA). The expression of miR-31, lysine demethylase 2A (KDM2A), E2F transcription factor 1 (E2F1), and pituitary tumor transforming gene 1 (PTTG1) was validated in cartilage tissues of knee OA patients. Following SMSC-EV extraction and identification, chondrocytes with the miR-31 inhibitor were added with SMSC-EVs, whereupon the effects of miR-31 on proliferation and migration of chondrocytes were assessed. The interaction among miR-31, KDM2A, E2F1, and PTTG1 in chondrocyte activities was probed in vitro, along with an in vivo mouse knee OA model. We identified downregulated miR-31, E2F1, and PTTG1 and upregulated KDM2A in cartilage tissues of knee OA patients. SMSC-EV-packaged miR-31 potentiated chondrocyte proliferation and migration as well as cartilage formation by targeting KDM2A. Mechanistically, KDM2A bound to the transcription factor E2F1 and inhibited its transcriptional activity. Enrichment of E2F1 in the PTTG1 promoter region activated PTTG1 transcription, accelerating chondrocyte proliferation and migration. SMSC-EVs and EVs from miR-31-overexpressed SMSCs alleviated cartilage damage and inflammation in knee joints in vivo. SMSC-EV-encapsulated miR-31 ameliorates knee OA via the KDM2A/E2F1/PTTG1 axis.

Study of bilateral elbow joint osteoarthritis treatment using conditioned medium from allogeneic adipose tissue-derived MSCs in Labrador retrievers

Canine elbow dysplasia is a common cause of forelimb lameness in dogs and can lead to development of osteoarthritis (OA). A potential alternative to pain management is the use of a safe cell-free based therapy through trophic and paracrine factors of mesenchymal stem cells (MSCs). The aim of study was to identify the profile of selected mediators of potential clinical relevance in synovial fluid (SF) samples of dogs with elbow OA and analyse the range of motion (ROM) before and after cell-free MSCs-based treatment. In this study, conditioned medium from allogeneic canine adipose tissue - derived MSC (CM-AD-MSC) was prepared and administered into both elbow joints with OA in six Labrador retriever dogs (n = 6) on day 0 and 14 without creating a control group with a placebo. The SF of the elbow joints was analysed for the presence of several biomolecules (IL-6, IL-10, IL-8, IL-2, IL-12, TNF-αIFN-γ, MMP-3TIMP-1) before and after intraarticular applications of CM-AD-MSC. Kinematic analysis was used to assess the clinical effect of CM-AD-MSC. Analyses of SF and ROM were performed on days 0, 14 and 42. Concentration levels of MMP-3, TIMP-1, IL-6 and TNF-α in SF showed significant differences before and after the treatment (P < .05). There was a significant improvement in ROM between day 0 and 42 (P < .001). No severe adverse events were observed during the study. Results support the potential supportive effect of CM-AD-MSC as a noninvasive therapeutic tool for pain management of OA elbow joints in dogs.

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.

Celecoxib Attenuates Cartilage Matrix Damage in Arthritis Rats by Inhibiting NF-κ B

Objective: Celecoxib selectively inhibits the activity of COX-2 and the production of prostaglandin (PG), and plays a therapeutic role in treating osteoarthritis (OA). NF-κB signaling and IL-1α and TNFα are involved in OA pathogenesis. This study explored whether Celecoxib might exert therapeutic effects on OA through regulating NF-κB signaling and IL-1β and TNF release in OA rat model. Method : The contents of MMP-13, Hyp, IL-1β and TNFα in synovial fluid were detected by ELISA. The protein expressions of NF-κ B p-p65, COL2A1 and the activity of caspase-3 were detected. OA model rats were separated into OA group and OA+ Celecoxib group followed by analysis of MMP-13, Hyp, IL-1β and TNF level in articular fluid by ELISA and p-p65 and COL2A1 level and caspase-3 activity by western blot. Rat cartilage tissue was cultured and divided into control group, LPS group and LPS+ Celecoxib group followed by analysis of expressions of p-p65 and COL2A1 in cartilage tissue, IL-1 and TNF content in culture supernatant, and chondrocyte apoptosis. Results: Compared with Sham group, p-p65 expression and caspase-3 activity in cartilage tissue of OA rats was increased and COL2A1 level was reduced. Meanwhile the expression of MMP-13, Hyp, IL-1β and TNF in articular fluid of OA rats was increased. Compared to OA group, p-p65 expression and caspase-3 activity was decreased and COL2A1 expression was increased in OA+ Celecoxib treatment group along with decreased MMP-13, Hyp, IL-1β and TNF level in articular fluid. p-p65 expression and caspase-3 activity in LPS group was increased and COL2A1 expression was decreased with increased IL-beta; and TNF content. Compared to LPS group, p-p65 expression and caspase-3 activity was decreased and COL2A1 expression was increased in LPS+ Celecoxib group with decreased content of IL-1β and TNFα. Conclusion: Celecoxib can protect cartilage in OA by inhibiting NF-κB activation and IL-1β and TNF release, and decreasing cell apoptosis in inflammatory environment.

The role and mechanism of S100 calcium binding protein B in osteoarthritis cartilage damage repair

To investigate the role and mechanism of S100 calcium binding protein B (S100B) in osteoarthritis (OA) cartilage damage repair. Twenty New Zealand rabbits were randomly divided into control group and model group, with 10 rabbits in each group. Rabbits in the model group were injured by the right knee joint immobilization method to make the artilage injury model, while the control group did not deal with any injury. After 4 weeks, the levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in synovial fluid were detected by ELISA method; the mRNA and protein expressions of S100B, fibroblast growth factor 2 (FGF-2), and FGF receptor 1 (FGFR1) in cartilage tissue were examined by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot assay. Human synovial fibroblasts (SF) were isolated and cultured in vitro. The effects of S100B overexpression and knockdown on the levels of IL-1β and TNF-α (ELISA method) and the expressions of FGF-2 and FGFR1 gene (qRT-PCR) and protein (Western blot) were observed. Moreover, the effects of FGFR1 knockdown in above S100 overexpression system on the levels of IL-1β and TNF-α (ELISA method) and the expressions of FGF-2 and FGFR1 gene (qRT-PCR) and protein (Western blot) were observed. ELISA detection showed that the expressions of IL-1β and TNF-α in the synovial fluid of the model group were significantly higher than those of the control group ( P<0.05); qRT-PCR and Western blot detection showed that the mRNA and protein expressions of S100B, FGF-2, and FGFR1 in cartilage tissue were significantly higher than those of the control group ( P<0.05). Overexpression and knockdown S100 could respectively significantly increase and decrease lipopolysaccharides (LPS) induced IL-1β and TNF-α levels elevation and the mRNA and protein expressions of FGF-2 and FGFR1 ( P<0.05); whereas FGFR1 knockdown could significantly decrease LPS induced IL-1β and TNF-α levels elevation and the mRNA and protein expressions of FGF-2 and FGFR1 ( P<0.05). S100B protein can regulate the inflammatory response of SF and may affect the repair of cartilage damage in OA, and the mechanism may be related to the activation of FGF-2/FGFR1 signaling pathway.

Effect of modified Qing Long Bai Wei needling on the levels of IL-1β, IL-6 and INF-α in synovial fluid of knee osteoarthritis patients

To compare the modified Qing Long Bai Wei needling method and ordinary acupuncture method in the effects of improving the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in the treatment of knee osteoarthritis (KOA), and to determine the advantage of the modified Qing Long Bai Wei needling method for KOA. One hundred KOA patients were randomized into a treatment group and a control group by using the random number table, with 50 cases in each group. The treatment group was intervened by the modified Qing Long Bai Wei needling method, and the control group was given ordinary acupuncture. The two groups were observed before and after the treatment to determine the changes in the levels of IL-1β, IL-6 and TNF-α in synovial fluid, and the clinical efficacies were compared between the two groups. The total effective rate and clinical recovery rate were 97.9% and 52.1% respectively in the treatment group, versus 85.1% and 25.5% in the control group, and the between-group differences were statistically significant (both P<0.01). After the treatment, the levels of IL-1β, IL-6 and TNF-α in synovial fluid changed significantly in both groups (all P<0.01); there were significant differences in the levels of IL-1β, IL-6 and TNF-α in synovial fluid between the two groups (all P<0.01). The modified Qing Long Bai Wei needling is an effective method for KOA and it can significantly improve the levels of IL-1β, IL-6 and TNF-α in synovial fluid.

Influence of acupotomy loosing on IL-6, IL-10 and TNF-α in synovial fluid of rheumatoid arthritis patients with elbow joint stiffness

ObjectiveTo compare differences of acupotomy loosing combined with medication treatment, electroacupuncture combined with medication treatment and simple medication treatment in effects on rheumatoid arthritis patients with elbow joint stiffness and investigate the anti-inflammatory mechanism of the acupotomy loosing. MethodsA total of 60 cases of rheumatoid arthritis (RA) patients with elbow joint stiffness were randomly assigned into the group receiving acupotomy loosing (group A), group with electroacupuncture (group B) and the one undergoing medication treatment (group C) with 20 cases for each group. Based on the medication treatment, all patients underwent continuous oral administration with Methotrexate (MTX), Leflunomide (LEF) and Bitongding capsules for 3 weeks. And no other treatments were given to group C. In addition to medications treatment, the electroacupuncture was performed in group B. The acupoints of Tiānzhù (天柱 BL 10), Dàzhuī (大椎 GV 14); Fēngchí (风池 GB 20), Qūchí (曲池 LI 11), Qūzé (曲泽 PC 3), Chĭzé (尺泽 LU 5), Shŏusānlĭ (手三里 LI 10), Xiăohăi (小海 SI 8), Shàohăi (少海 HT 3), Tiānjĭng (天井 TE 10), Qīnglĕngyuān (清冷渊 TE 11) and Hégŭ (合谷 LI 4) in the affected side were selected. A pair of electrodes were connected to LI 11 and LI 10, and another pair of electrodes were connected to PC 3 and LU 5, and the continuous wave with frequency of 2 Hz was designed, the needle retention for 30 min was performed, and the acupuncture was performed for 6 times per week with 3 weeks for one course, and there was one course totally. Besides the medication treatment, group A underwent the acupotomy loosing therapy. The tender point in lateral elbow joint, etc. were taken as the treatment point, and 6–8 treatment points being taken for each time, and longitudinal dredging and transverse exfoliation were conducted for 2–3 times with the acupotomy. The treatment was given for one time per week with three weeks for one course, and there was one course totally. The changes of maximum angle of active extension position, maximum angle of active flexion position and range of motion were observed, and levels of IL-6, IL-10 and TNF-α in affected synovial fluid of elbow joint were tested before the treatment and 2 weeks after the treatment in the groups. Results① Compared with those before treatment, the maximum angle of active extension position were smaller, the maximum angle of active flexion position were larger and the range of motion were wider of the affected elbow joints of the patients in the 3 groups on the 2 weeks after the treatment. There were statistical significances for the differences (All P < 0.05). Two weeks after the treatment, as compared with those in group C, the affected elbow joint for patients in the group B and group A was smaller in maximum angle of active extension position, larger in maximum angle of active flexion position and wider in range of motion and there were statistical significances for the differences (All P < 0.05). Comparing with those in the group B, the affected elbow joint for patients in the group A was smaller in maximum angle of active extension position, larger in maximum angle of active flexion position and wider in range of motion and there were the statistical significances for the differences (All P < 0.05). ② Compared with those before treatment, the levels of TNF-α and IL-6 were lower and the level of IL-10 was higher of the 3 groups on the 2 weeks after the treatment. There were the statistical significances for the differences (All P <0.05). For 2 weeks after the treatment, compared with those in the group C, group B and group A were lower in levels of TNF-α and IL-6 and higher in level of IL-10 and there were the statistical significances for the differences (All P < 0.05). As compared with those in the group B, group A was lower in levels of TNF-α and IL-6 and higher in level of IL-10 and there were the statistical significances for the differences (All P < 0.05). ConclusionsThe combination of acupotomy loosing can improve the maximum angle of active extension position, maximum angle of active flexion position and range of motion in affected elbow joint for RA patients with elbow joint stiffness, whose efficacy was superior to single basic treatment and electroacupuncture combined with basic treatment. Meanwhile, the levels of proinflammatory cytokines, such as TNF-α and IL-6 can be decreased, and the level of anti-inflammatory cytokines, such as IL-10 can be increased, playing a role in regulating the imbalance between proinflammatory cytokines and anti-inflammatory cytokines in RA patients, which may be one of mechanisms regarding treating RA and improving the range of motion for stiff joints.

Study the relevance between inflammatory factors and estradiol and their association with knee osteoarthritis in postmenopausal women.

To investigate whether serum levels of inflammatory factors and estradiol (E2) are involved in the pathogenesis of postmenopausal women with knee osteoarthritis (OA). 58 randomly patients diagnosed with postmenopausal knee OA that underwent orthopedic surgery from October 2013 to October 2016 in our hospital were selected. These patients, considered as the experimental group, according to the degree of cartilage damage, were divided into light, medium and heavy groups. 58 patients with menstrual disorders without knee OA were in the control group. 35 cases without osteoarthritis were included in the normal control group. Serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), erythrocyte sedimentation rate (ESR), high sensitive C- reactive protein (CRP), estradiol (E2) and IL-1, IL-6 and TNF-α levels in the synovial fluid of the experimental group were measured. The serum levels of IL-1, IL-6, TNF-α, and CRP in the normal control group, the control group and the experimental group were gradually increasing, the difference was statistically significant (p<0.05). The level of serum E2 was gradually decreasing (p<0.05); the difference of ESR between normal control group and control group had no significant difference (p>0.05), but the level of ESR in experimental group was higher than the normal control group and the control group (p<0.05). The serum levels of IL-1, TNF-α in experimental group of mild, moderate and severe sub-group were gradually increasing, the difference was statistically significant (p<0.05); while the level of IL-6 in the early, middle stage of OA increased significantly, and the late was reduced (p<0.05). The level of E2 was gradually decreased in the mild, moderate and severe sub-group of the experimental group, which had statistically significant difference (p<0.05). The level of serum E2 in the experimental group was positively correlated with the levels of IL-1, IL-6 and TNF-α in synovial fluid (p<0.05). The lack of estradiol is associated with the pathogenesis of OA in postmenopausal women, the inflammatory factors of IL-1, IL-6, TNF-α in postmenopausal increased in serum and synovial fluid may promote and aggravate the OA.

The expression and significance of interleukin-1β and tumor necrosis factor-α in synovial fluid of patients with knee osteoarthritis

Objective To detect expression level of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in synovial fluid of patients with knee osteoarthritis, and the significance. Methods From May 2012 to May 2016, 60 patients with knee osteoarthritis were admitted in our department as observation group, and on the basis of severity, three subgroups were set up: moderate severe subgroup (n=16), severe subgroup (n=18), very severe subgroup (n=17), and extreme subgroup (n=9). Twenty patients without osteoarthritis at the same period served as the control group. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of IL-1β and TNF-α. Results IL-1β concentrations in the control group, moderate severe subgroup, severe subgroup, and very severe subgroup and extreme severe subgroup were (9.823±1.286), (11.885±1.206), (13.571±2.052), (18.783±4.372), and (27.109±4.901) pg/ml, and TNF-α concentrations were (10.281±2.118), (13.807±4.208), (17.815±4.689), (20.425±6.335) and (21.722±7.924) pg/ml. The concentration of TNF-α and IL-1β of serious group, very serious group and extremely severe group were greater than the control group and the difference is statistically significant (P= 0.000); And the concentration of IL-1β of serious group, very serious group and extremely severe group increase in turn and has significant difference (F= 61.296, P= 0.000); The concentration of very serious group, extremely severe group is greater than the severe group, and the difference is statistically significant (F= 18.291, P= 0.000); The concentration of TNF-α and IL-1β shows increasing trend, as patients severity increased and positively related to the degree of disease (r= 0.850, P= 0.000; r= 0.849, P= 0.000). Conclusion The expression levels of IL-1β and TNF-α in synovial fluid of patients with knee osteoarthritis increase significantly, playing an important role in the onset and progression of the process. Key words: Knee osteoarthritis; Interleukin-1β; Tumor necrosis factor-α; Joint synovial fluid

Improvement in orthopedic outcome score and reduction in IL-1β, CXCL13, and TNF-α in synovial fluid of osteoarthritis patients following arthroscopic knee surgery.

Knee osteoarthritis (KOA) is a common degenerative joint disease and immune system dysregulation has been implicated in its pathogenesis. The effect of arthroscopic knee surgery, an important method for KOA diagnosis and treatment, on the expression of immune regulators remains poorly understood. We aimed to investigate the clinical efficacy of such surgery and its impact on IL-1β, CXCL13, and TNF-α expression in the knee joint synovial fluid of osteoarthritis patients. Fifty-seven patients having undergone arthroscopic knee surgery in our hospital were included. Visual analog scale (VAS) and Lysholm scores were recorded before surgery, and knee joint synovial fluid was collected during the procedure. According to Outerbridge cartilage damage score (grade 0, 1, 2, 3, or 4), patients were divided into five groups. In addition, VAS and Lysholm scores were recorded and knee joint synovial fluid was collected after a six-month follow-up period. Expression of IL-1β, CXCL13, and TNF-α in synovial fluid samples was then measured. In each group, levels of these molecules and VAS and Lysholm scores were significantly lower after surgery (P < 0.05). IL-1β, CXCL13, and TNF-α levels were significantly elevated in patients with higher cartilage damage scores compared to those with lower scores. Arthroscopic knee surgery can reduce IL-1β, CXCL13, and TNF-α levels in the knee joint synovial fluid of osteoarthritis patients. Moreover, reduced presence of these molecules correlates with clinical improvement of this condition. Therefore, reduction in IL-1β, CXCL13, and TNF-α expression might be used as a factor for long-term osteoarthritis prognosis.

Serum and knee synovial fluid matrixmetalloproteinase-13 and tumor necrosis factor-alpha levels in patients with late stage osteoarthritis

ObjectiveTo compare the levels of MMP-13 and TNF-α in late stage osteoarthritis, define their predominant pathways and investigate their correlation with McMaster Universities Arthritis Index scores. Patients and methodsA total of 42 patients (mean age 64 ± 8.8) with grade 3 and grade 4 knee osteoarthritis according to Kellegren- Lawrence criteria and who were scheduled for total knee arthroplasty were enrolled in the study. TNF-alpha and MMP-13 levels were measured preoperatively from venous blood samples and intraoperatively from knee synovial fluid via ELISA. Preoperative and 1 month postoperative knee functions were assessed by McMaster Universities Arthritis Index. ResultsGrade 4 synovial fluid MMP-13 (4.76 ± 5.82) was elevated compared to grade 3 (3.95 ± 4.45) (p = 0.438), whereas grade 3 serum MMP-13 (1.128 ± 0.308) was found elevated compared to grade 4 (1.038 ± 0.204) (p = 0.430). Grade 4 serum TNF-α (0.253 ± 0.277) was elevated compared to grade 3 (0.206 ± 0.219) whereas grade 3 synovial fluid TNF-α (0.129 ± 0.052) was elevated compared to grade 4 (0.118 ± 0.014). Positive correlation was observed between synovial fluid MMP-13 levels and postoperative WOMAC scores. Mean serum TNF-α level (0.226 ± 0.246 pg/ml) was found higher compared to synovial level (0.124 ± 1.59), synovial MMP-13 level (4.31 ± 1.24) was found higher compared to serum level (1.089 ± 1.519). ConclusionDespite the systemic increase in TNF-α levels concordant with osteoarthritis grade, MMP-13 levels are elevated via local manner with a significant correlation with WOMAC scores. Level of evidenceLevel IV, Diagnostic study.

TNF-α concentrations in pre-operative synovial fluid for predicting early post-operative function and pain after fast-track total knee arthroplasty

BackgroundTumor necrosis factor-alpha (TNF-α) helps regulate neuroinflammation and anxiety and could conceivable predict early post-operative pain and function after fast-track total knee arthroplasty (TKA). MethodsIn patients with severe osteoarthritic knees undergoing TKA, we assessed: the correlations between pre-operative concentrations of TNF-α in synovial fluid; pre- and six-week post-operative knee function and pain; pre- and post-operative anxiety; pre- and post-operative synovial fluid concentrations of cartilage oligomeric matrix protein (COMP); age and body mass index (BMI). ResultsOf 100 enrolled patients, 78 had evaluable TNF-α data, and 58 had evaluable COMP data. Pre-operative TNF-α concentrations were inversely correlated with post-operative pain scores during walking (rS=−0.26, P=0.03) and with change of pain at rest during six weeks after TKA (rs=−0.28, P=0.03) and were directly correlated with a higher post-operative Knee Society score (KSS) (rS=0.43, P<0.001) and with greater increases in this score during six weeks after TKA (rS=0.33, P=0.001). Mean TNF-α concentrations were higher in the 39 patients reporting any pre-operative pain at rest than in 36 patients reporting no pre-operative pain (P=0.015) and were the only independent predictor of pre-operative pain at rest (OR=13, P=0.02). Independent predictors of better post-operative knee function were higher log-transformed TNF-α concentrations (β=0.38, P=0.002) and male sex (β=0.28, P=0.02). ConclusionsHigh levels of pre-operative TNF-α concentrations could be used as an independent predictor of better knee function at six weeks of follow-up. In patients with lower pre-operative TNF-α concentrations, post-operative pain management may improve the early outcome of the operated joint.

A Prospective Study on Inflammatory Cytokines and Bone Metabolism Mediators in Patients Affected by Rheumatoid and Psoriatic Arthritis treated with Adalimumab

Rheumatoid (RA) and Psoriatic arthritis (PsA) are characterized by extensive synovitis resulting in bone destruction in both diseases and new bone formation in PsA. Objective: This prospective study analyzed interleukin (IL)-6, IL-17, IL-23, tumor necrosis factor (TNF)-α serum and synovial fluid (SF) levels and osteoprotegerin (OPG), bone-specific alkaline phosphatase (BAP) and D-vitamin (D-Vit) serum levels in RA and PsA patients before and after anti-TNF-α. Methods: 15 RA and 15 PsA patients with knee effusion and starting adalimumab (ADA) treatment were enrolled. Serum and SF from inflamed knee joint samples were obtained at baseline and after 24 weeks of treatment. Statistical analysis was performed using Graph Pad 5.0 statistical software. Results: In RA and PsA, SF IL-6, IL-17, and TNF-α were higher than serum levels while higher serum IL-23 was detected than in SF. Higher serum/SF IL-6, IL-23 and SF TNF-α were observed in RA than PsA, while serum IL-17 was higher in PsA than RA. Positive feedback among IL-6, IL-23, IL-17 and CRP and negative correlation between IL-17 and TNF-α in RA were found. In PsA, IL-23 correlated positively with IL-6. OPG correlated positively with ESR/CRP in RA and PsA. D-Vit correlated negatively with OPG and ESR in PsA. Higher BAP in RA than PsA and positive correlation with IL-6 in RA and with OPG in PsA were noticed. In PsA, IL-6 and OPG serum levels decreased significantly after 24 weeks ADA treatment. Conclusions: Distinct distribution of inflammatory cytokines and correlations with bone mediators were detected in RA and PsA. ADA affected inflammatory cytokines and bone mediators in PsA patients.