The small molecule NSM00191 specifically represses the TNF-α/NF-кB axis in foot and ankle rheumatoid arthritis

A szerzők összefoglaló közleményükben az irodalmi adatok figyelembevételével áttekintik a rheumatoid arthritis primer és szekunder pulmonalis szövődményeit. A rheumatoid arthritis gyógyszeres terápiájának pulmonológiai szövődményei közül kiemelik a betegségmódosító antireumatikus szereket, amelyek közül kitérnek a methotrexat indukálta tüdőgyógyászati kórképekre. A methotrexat szinte majdnem minden additív hatású kettős és hármas – O’Dell-séma – kombinációs terápiában szerepel, ezért is fontos e gyógyszer okozta pulmonalis szövődmények időben történő felismerése. A reumatológusok számára egyre nagyobb kihívást jelent a methotrexattal szemben rezisztens rheumatoid arthritis kezelése. A biológiai terápiás szerek citokinantagonistaként, TNF-α-blokkolás révén fejtik ki hatásukat, és a betegségmódosító antireumatikus szerekhez képest hatásosabban tudják fékezni a betegség progresszióját. Ezek a biológiai válaszmódosító szerek. Főbb képviselőik az infliximab, az adalimumab és az etanercept. A szerzők végül foglalkoznak a biológiai válaszmódosító szerek okozta szekunder pulmonalis szövődményekkel: a pulmonalis tuberculosissal, a bakteriális tracheobronchitisszel, a bakteriális pneumoniával, bronchiectasiával és pulmonalis oedemával, a rapid progresszív fibrotizáló alveolitisszel, valamint a coccidiomycosissal. Az Arizona, Kalifornia, Nevada területén élő, biológiai válaszmódosító szerekkel végzett terápiában részesülő rheumatoid arthritises betegek mintegy 3%-ánál várható a 15%-os halálozással járó pulmonalis és szisztémás gombafertőzés – coccidiomycosis – kialakulása. A gyakori földrengések következtében a talajból a légtérbe kerülő spórák betegítik meg a gyógyszeres terápia miatt immunszupprimált egyéneket. A szerzők felhívják a figyelmet, hogy az előbb említett endémiás, valamint egyéb földrengésaktív területre utazó, biológiai terápiában részesülő betegek potenciális fertőzésveszélynek vannak kitéve, amely miatt a betegek ez irányú tájékoztatása a kezelőorvos részéről elengedhetetlen. A biológiai válaszmódosító szerek újabb és újabb csoportjainak kipróbálása és felhasználása a közeljövőben várható rheumatoid arthritisben. Jelenleg a TNF-α-gátló kezelésre nem reagáló betegeknél lehetőség van a non-Hodgkin-lymphoma terápiájában használatos B-lymphocyta-gátló rituximab alkalmazására. Ez utóbbi citokin rheumatoid arthritisben történő felhasználása során észlelt pulmonalis szövődményeiről még nem rendelkezünk elegendő ismerettel. Napjaink antireumatikus terápiái a betegek életminőségének jelentős javulását eredményezik, miközben az egyre korszerűbb kezelési módok a pulmonalis szövődmények körét gyarapítják.

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Genetic Variation in TNF-α, its Relation with Inflammatory Biomarkers and Susceptibility to Rheumatoid Arthritis

Annals of Immunology & Immunotherapy ◽

10.23880/aii-16000122 ◽

2020 ◽

Vol 2 (2) ◽

Author(s):

Khadiga Ahmed Ismail

Keyword(s):

Rheumatoid Arthritis ◽

Serum Level ◽

Functional Disability ◽

Serum Levels ◽

Amplification Refractory Mutation System ◽

Reactive Protein ◽

Tnf Α ◽

Mutation System ◽

Potential Factor ◽

Factor Α

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.

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Evaluating the efficacy of intra-articular injections of platelet rich plasma (PRP) in rheumatoid arthritis patients and its impact on inflammatory cytokines, disease activity and quality of life.

Current Rheumatology Reviews ◽

10.2174/1573397116666201113090629 ◽

2020 ◽

Vol 16 ◽

Author(s):

Dalia S. Saif ◽

Nagwa N. Hegazy ◽

Enas S. Zahran

Keyword(s):

Quality Of Life ◽

Rheumatoid Arthritis ◽

Disease Activity ◽

Inflammatory Cytokines ◽

Platelet Rich Plasma ◽

Joint Inflammation ◽

Monthly Interval ◽

Post Injection ◽

Tnf Α

Background: Among rheumatoid arthritis patients (RA), general disease activity is well regulated by diseasemodifying anti-rheumatic medications (DMARDS), but sometimes local inflammation still persists among a few joints. Adjuvant modern molecular interventions as Platelet Rich Plasma (PRP) with a suggested down regulating effect on inflammatory mediators has a proven effect in management of RA. We aim to evaluate the therapeutic effect of intra-articular PRP versus steroid in RA patients and their impact on inflammatory cytokines IL1B , TNF α, local joint inflammation, disease activity and quality of life (QL). Methods: Open labeled parallel randomized control clinical trial was carried out on 60 RA patients randomly divided into 2 groups, Group 1: included 30 patients received 3 intra-articular injections of PRP at monthly interval, Group 2: included 30 patients received single intra-articular injection of steroid. They were subjected to clinical, laboratory, serum IL1B and TNF α assessment at baseline and at 3, 6 months post injection. Results: Patients of both groups showed improvements in their scores of evaluating tools at 3months post injection and this improvement was persistent in the PRP group up to 6 months post injection while it was continued only for 3 months in the steroid group. Conclusions: PRP is a safe, effective and useful therapy in treating RA patients who had insufficient response and persistent pain and inflammation in just one or two joints through its down regulating effect on inflammatory cytokines IL1B, TNF α with subsequent improvement of local joint inflammation, disease activity and QL.

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Can Cytokines be used as an Activation Marker in Rheumatoid Arthritis?

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666201019115030 ◽

2020 ◽

Vol 20 ◽

Author(s):

Fatih Öner Kaya ◽

Yeşim Ceylaner ◽

Belkız Öngen İpek ◽

Zeynep Güneş Özünal ◽

Gülbüz Sezgin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Healthy Volunteers ◽

Venous Blood ◽

Cross Sectional Study ◽

Joint Disease ◽

Control Group ◽

Cross Sectional ◽

Positive Correlation ◽

Das 28 ◽

Tnf Α

Aims: The etiopathogenesis of Rheumatoid Arthritis (RA) is not clearly understood. However, the role of the cytokines takes an important part in this mechanism. We aimed to bring a new approach to the concept of 'remission' in patients with RA. Background: RA is a chronic, autoimmune, inflammatory disease that involves small joints in the form of symmetrical polyarthritis and progresses with exacerbations and remissions. Pain, swelling, tenderness and morning stiffness are typical of the joints involved. Although it is approached as a primary joint disease, a wide variety of extra-articular involvements may also occur. It is an interesting pathophysiological process, the exact cause of which is still unknown, with many environmental, genetic and potentially undiscovered possible factors in a chaotic manner. Objective: In this cross-sectional study, sedimentation rate (ESR), C- Reactive protein (CRP), Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and IL-10 were measured in three groups which were healthy volunteers, patients with RA in the active period, and patients with RA in remission. Disease activity score-28 (DAS-28) was calculated in active RA and RA in remission. Methods: This study included 20 healthy volunteers, 20 remission patients with RA and 20 active RA patients. Venous blood samples were collected from patients in both healthy and RA groups. Results: RA group consisted 43 (71.6%) female and 17 (28.4%) male. Control group consisted 11 (55%) female and 9 (45%) male. TNF-R was significantly high only in the active group according to the healthy group (p=0.002). IL-10 was significantly high in active RA according to RA in remission (p=0.03). DAS-28 was significantly high in active RA according to RA in remission (p=0.001). In the active RA group, ESR and TNF-R had a positive correlation (r:0.442; p=0.048). In the active RA group, there was also a positive correlation between TNF-R and CRP (r:0.621; p=0,003). Both healthy and active RA group had significant positive correlation between ESR and CRP (r: 0.481; p=0.032 and r: 0,697; p=0,001 respectively). Conclusion: TNF-R can be the main pathophysiological factor and a marker showing activation. TNF-R can be very important in revealing the effect of TNF on the disease and the value of this effect in the treatment and ensuring the follow-up of the disease with CRP instead of ESR in activation.

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Serum IL-35 is decreased in overweight patients with rheumatoid arthritis: its correlation with Th1/Th2/Th17-related cytokines

BMC Immunology ◽

10.1186/s12865-021-00431-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yuxuan Li ◽

Yang Jie ◽

Xiaofei Wang ◽

Jing Lu

Keyword(s):

Rheumatoid Arthritis ◽

Medical Records ◽

Clinical Information ◽

Serum Cytokines ◽

Healthy Donors ◽

Potential Biomarker ◽

Tnf Α ◽

Ifn Γ ◽

Quantitative Changes ◽

Anti Inflammatory Cytokine

Abstract Background Obesity is correlated with worse drug responses and high disease activity in patients with rheumatoid arthritis (RA). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that mainly produced by regulatory T (Treg). This study was performed to analyze whether IL-35 was correlated with obesity in RA and investigate the correlation between other Th1/Th2/Th17-related cytokines and obesity in RA. Results The serum IL-35 level was analyzed in RA (n = 81) and healthy donors (n = 53) by ELISA assay, and was compared between three groups (body mass index (BMI) < 18.5,≥18.5 to 25, > 25). Serum cytokines including IL-2, IL-4, IL-10, IL-17, INF-γ, TNF-α levels were measured using Flowcytometry assay. Clinical information was extracted from medical records. Serum IL-35 level in overweight patients were significantly decreased than those in lean patients. Furthermore, Th1/Th2/Th17-related cytokines from overweight patients with RA showed the characteristic immunological features. Serum IL-6, IL-17 and TNF-α levels were positively correlated with BMI. However, serum IL-2, IL-4, IL-10 and IFN-γ concentrations were not correlated with BMI. Conclusions Quantitative changes in serum IL-35 level were characteristic in overweight patients with RA. These findings indicate that IL-35 plays an important role in the development of RA and may prove to be a potential biomarker of active RA.

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Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

International Journal of Molecular Sciences ◽

10.3390/ijms22031022 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1022

Author(s):

Tatyana P. Makalish ◽

Ilya O. Golovkin ◽

Volodymyr V. Oberemok ◽

Kateryna V. Laikova ◽

Zenure Z. Temirova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Rat Model ◽

Peripheral Blood ◽

Antisense Oligonucleotide ◽

Joint Inflammation ◽

Blood Concentrations ◽

Tnf Α ◽

Effective Drugs ◽

First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

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AB0051 THE EFFECTS OF NON-INVASIVE VAGUS NERVE STIMULATION ON IMMUNOLOGICAL RESPONSES AND PATIENT REPORTED OUTCOME MEASURES OF FATIGUE IN PATIENTS WITH CHRONIC FATIGUE SYNDROME, FIBROMYALGIA, AND RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1999 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1057.3-1058

Author(s):

E. Traianos ◽

B. Dibnah ◽

D. Lendrem ◽

Y. Clark ◽

V. Macrae ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Daytime Sleepiness ◽

Vagus Nerve Stimulation ◽

Chronic Fatigue ◽

Patient Reported Outcome Measures ◽

Patient Reported Outcome ◽

Physical Fatigue ◽

Fatigue Syndrome ◽

Tnf Α ◽

Patient Reported

Background:Fatigue is reported as a common symptom among autoimmune and other chronic diseases such as fibromyalgia (FM), a long-term condition with uncertain pathophysiology. Previous studies from our group suggest that non-invasive vagus nerve stimulation (nVNS) may contribute to the improvement of patient reported outcome measures (PROMs) of fatigue in patients with primary Sjögren’s Syndrome (1).Objectives:This follow-up study uses the gammaCore device (electroCore) to assess the effect of nVNS on PROMs of fatigue and immune responses in chronic fatigue syndrome (CFS), FM and rheumatoid arthritis (RA).Methods:The study included thirteen CFS, fourteen FM and fifteen RA patients who used the gammaCore nVNS device twice daily over a 26-day period. Pre- and post- nVNS bloods were drawn at baseline and final visits. Whole blood samples were stimulated with 2 ng/mL lipopolysaccharide (LPS) and the IL-6 and TNF-α cytokine concentrations were quantified at 24 hours. In addition, the epidermal growth factor (EGF), IFN-γ, IL-6, IP-10, MIP-1α, and TNF-α levels were measured in ‘pre-nVNS’ serum and flow cytometric profiles of whole blood immune cells were analysed. The patient reported outcome measures (PROMs) recorded at each visit were the Visual Analogue Scale (VAS) (0-100 cm) of abnormal fatigue, Hospital Anxiety and Depression (HAD) Scale, Orthostatic Grading Scale, Epworth Sleepiness Scale (daytime sleepiness), and Profile of fatigue (PRO-F) for Physical and Mental fatigue. Paired t-tests were performed to assess for changes in PROMs, cytokine levels, and cell subset distribution and associations of cytokine response with PROMs were investigated by correlation analyses.Results:Eleven CFS, twelve FM and fourteen RA patients completed the study. There was a significant reduction in daytime sleepiness in CFS (p =0.0321) and FM (p =0.0294) patients between the final and baseline visits and a significant reduction in HAD depression (p =0.0413) in FM (Fig.1). Improvement in VAS for abnormal fatigue, HAD-Anxiety, HAD-Depression, PRO-F Physical and Mental fatigue was observed in all three groups over the study period with a reduction in VAS fatigue in 64% of CFS, 67% of FM and 62% of RA patients. There were no significant changes in the immune cell subsets or in cytokine response. Finally, higher baseline pre-nVNS supernatant IL-6 levels were predictive of an improvement in VAS fatigue (p =0.0006), Daytime Sleepiness (p =0.0466) and PRO-F Physical fatigue (p =0.0196) in RA, while higher baseline TNF-α levels were predictive of an improvement in VAS fatigue (p =0.0003), Daytime Sleepiness (p =0.0380), Orthostatic (p =0.0281) and PRO-F Physical fatigue (p =0.0007) in FM.Conclusion:Our findings suggest that nVNS may contribute to the improvement of PROMs of fatigue in CFS, FM and RA. NVNS led to significant reductions in daytime sleepiness in CFS and FM, and depression in FM. Further studies and a larger sample size are needed to investigate the potential effects of nVNS on diseases characterised by persistent fatigue.References:[1]Tarn J, Legg S, Mitchell S, Simon B, Ng WF. The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue and Immune Responses in Patients With Primary Sjögren’s Syndrome. Neuromodulation Technol Neural Interface. 2018;22(5):580–5.Figure 1.VAS for abnormal fatigue and PROMs recorded at baseline and final visits in patients with chronic fatigue syndrome (CFS), fibromyalgia (FM) and rheumatoid arthritis (RA). Boxplots show the median, upper, and lower quartiles for PROMs at visit 1 and visit 3 in each disease group. Paired-t tests revealed a significant reduction in daytime sleepiness in CFS and FM (B), and a significant reduction in HAD depression in FM (E). Improvement trends were observed in VAS for abnormal fatigue, HAD-Anxiety, HAD-Depression, PRO-F Physical fatigue and PRO-F Mental fatigue in all three groups over the 26-day study period.Acknowledgements:This study received infrastructural support from the National Institute of Health Research (NIHR) Newcastle Biomedical Research Centre at Newcastle Hospitals Foundation Trust and Newcastle University.Disclosure of Interests:Emmanuella Traianos: None declared, Bethany Dibnah: None declared, Dennis Lendrem: None declared, Yasmin Clark: None declared, Victoria Macrae: None declared, Victoria Slater: None declared, Karl Wood: None declared, David Storey: None declared, Bruce Simon Shareholder of: Bruce Simon is an employee and shareholder of electroCore., Employee of: electroCore, Inc., Justyna Blake Shareholder of: Justyna Blake is an employee of electroCore, and receives stock ownership., Employee of: electroCore, Inc., Jessica Tarn: None declared, Wan Fai Ng: None declared

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TNF-α Blockers Showed Prophylactic Effects in Preventing COVID-19 in Patients with Rheumatoid Arthritis and Seronegative Spondyloarthropathies: A Case–Control Study

Rheumatology and Therapy ◽

10.1007/s40744-021-00342-8 ◽

2021 ◽

Author(s):

Mansour Salesi ◽

Behrokh Shojaie ◽

Ziba Farajzadegan ◽

Naghmeh Salesi ◽

Erfan Mohammadi

Keyword(s):

Rheumatoid Arthritis ◽

Case Control Study ◽

Case Control ◽

Tnf Α ◽

Seronegative Spondyloarthropathies ◽

Control Study

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Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells

Life ◽

10.3390/life11060587 ◽

2021 ◽

Vol 11 (6) ◽

pp. 587

Author(s):

Fu-Tzu Pai ◽

Cheng-You Lu ◽

Chia-Hsin Lin ◽

John Wang ◽

Ming-Cheng Huang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Suppressor Cells ◽

Clinical Severity ◽

Histopathological Analysis ◽

Human Rheumatoid Arthritis ◽

Psoralea Corylifolia ◽

Collagen Induced Arthritis ◽

Tnf Α ◽

Synovial Tissues ◽

Orthopedic Diseases

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22–49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

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