scholarly journals The Micro-Immunotherapy Medicine 2LARTH® Reduces Inflammation and Symptoms of Rheumatoid Arthritis In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Ilaria Floris ◽  
Víctor García-González ◽  
Belen Palomares ◽  
Kurt Appel ◽  
Beatrice Lejeune
Keyword(s):  
Rheumatoid Arthritis ◽  
Histological Analysis ◽  
Pure Water ◽  
Joint Destruction ◽  
Clinical Signs ◽  
Clinical Score ◽  
Type Ii Collagen ◽  
Joint Disease ◽  
Paw Edema

Background. Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damages as well as pain and disability. In order to prevent disease progression, reduce pain, and major symptoms of RA, one good strategy consists in targeting proinflammatory cytokines that have the key role in the vicious circle of synovial inflammation and pain. The micro-immunotherapy medicine (MIM) 2LARTH® targets cytokines involved in inflammation. Aim. The aim of the study is to evaluate the effect of the MIM compared to vehicle in an in vivo model of RA, induced in mice after immunization with articular bovine type II collagen. Methods. Vehicle and MIM were dissolved in pure water (1 capsule in 100 ml) and 100 µl was given by gavage daily for 14 days. To evaluate the severity of arthritis, wrist and ankle thickness was determined, paw edema was measured, and a clinical score from 0 to 4 was established. Furthermore, histological analysis was performed. To evaluate systemic inflammation, circulating levels of IL-1β and TNF-α were measured by ELISA. Results. Ankle thickness was found to be significantly reduced in MIM-treated mice compared to vehicle-treated mice (P<0.05) and compared to untreated me (P<0.01). Paw edema was reduced, as well as clinical score attributed to MIM-treated mice in comparison with vehicle-treated mice and untreated CIA mice (P<0.01). In line with these results, histological analysis confirmed that MIM reduced inflammation and joint destruction in comparison to controls. No significant changes were found in plasmatic IL-1β levels between CIA and controls, while the levels of TNF-α significantly increased in the CIA group, and were lowered in MIM-treated mice (P<0.05 vs. vehicle and vs. CIA). Conclusion. The results indicate that the tested medicine reduces inflammation, histological, and clinical signs of RA in a CIA model.

Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 21 (8) ◽  
pp. 734-740 ◽  
Author(s):  
Shou-di He ◽  
Ning Tan ◽  
Chen-xia Sun ◽  
Kang-han Liao ◽  
Hui-jun Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Inflammatory Processes ◽  
Related Proteins ◽  
Local Stimulation ◽  
Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

scholarly journals The Novel Role of MIF in the Secretion of IL-25, IL-31, and IL-33 from PBMC of Patients with Rheumatoid Arthritis

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4968
Author(s):  
Samuel García-Arellano ◽  
Luis Alexis Hernández-Palma ◽  
Sergio Cerpa-Cruz ◽  
Gabriela Athziri Sánchez-Zuno ◽  
Melva Guadalupe Herrera-Godina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Joint Destruction ◽  
Study Groups ◽  
Joint Disease ◽  
The Novel ◽  
Peripheral Blood Mononuclear ◽  
Cytokine Dysregulation ◽  
New Evidence

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.

Drops of Lactiplantibacillus plantarum CRL 759 culture supernatant attenuates eyes inflammation induced by lipopolysaccharide

2021 ◽  
pp. 1-12
Author(s):  
B.I. Layús ◽  
M.A. Gomez ◽  
S.I. Cazorla ◽  
A.V. Rodriguez
Keyword(s):  
Inflammatory Diseases ◽  
Clinical Signs ◽  
Thiobarbituric Acid ◽  
Clinical Score ◽  
Ocular Inflammation ◽  
Retinal Cell ◽  
In Vitro Assays ◽  
Necrosis Factor Alpha

Anti-inflammatory effect of soluble secreted compounds of probiotic bacteria was widely demonstrated as therapy for different inflammatory diseases, but was not investigated in inflammatory eye disorders. The aim of this study was to determine whether Lactiplantibacillus plantarum CRL759 cell-free supernatant reduced inflammatory parameters and clinical signs in ocular inflammations. First, we evaluated the effect of L. plantarum CRL759 supernatant in vitro on human retinal cell line, ARPE-19 cells, stimulated with lipopolysaccharide (LPS). Then, we investigated in vivo its capacity to decrease inflammation by local administration on the eyes of mice with endotoxin induced inflammation. In vitro assays demonstrated that L. plantarum CRL759 supernatant reduced the production of interleukin (IL)-6, IL-8, nitric oxide and thiobarbituric acid reactive substances in LPS-stimulated ARPE-19 cells. Our in vivo data proved that L. plantarum supernatant significantly reduced the clinical score of endotoxin treated mice and diminished levels of tumour necrosis factor alpha, interferon gamma and protein concentration in aqueous humour. Histological examination showed reduction of infiltrating inflammatory cells in the posterior segment of the eyes. As far as we know, this is the first report showing that Lactobacillus spp. supernatant administered as drops reduces some parameters of ocular inflammation. This promising strategy is safe and could alleviate symptoms and signs of ocular inflammation in people that are refractories to the conventional therapies.

scholarly journals Elevated APE1/Ref-1 Levels of Synovial Fluids in Patients with Rheumatoid Arthritis: Reflection of Disease Activity

2021 ◽  
Vol 10 (22) ◽  
pp. 5324
Author(s):  
In Seol Yoo ◽  
Yu-Ran Lee ◽  
Seong Wook Kang ◽  
Jinhyun Kim ◽  
Hee-Kyoung Joo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Inflammatory Responses ◽  
Joint Destruction ◽  
Joint Inflammation ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Control ◽  
The Relationship

There is growing evidence that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) regulates inflammatory responses. Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized with synovitis and joint destruction. Therefore, this study was planned to investigate the relationship between APE1/Ref-1 and RA. Serum and synovial fluid (SF) were collected from 46 patients with RA, 45 patients with osteoarthritis (OA), and 30 healthy control (HC) patients. The concentration of APE1/Ref-1 in serum or SF was measured using the sandwich enzyme-linked immunosorbent assay (ELISA). The disease activity in RA patients was measured using the 28-joint disease activity score (DAS28). The serum APE1/Ref-1 levels in RA patients were significantly increased compared to HC and OA patients (0.44 ± 0.39 ng/mL for RA group vs. 0.19 ± 0.14 ng/mL for HC group, p < 0.05 and vs. 0.19 ± 0.11 ng/mL for OA group, p < 0.05). Likewise, the APE1/Ref-1 levels of SF in RA patients were also significantly increased compared to OA patients (0.68 ± 0.30 ng/mL for RA group vs. 0.31 ± 0.12 ng/mL for OA group, p < 0.001). The APE1/Ref-1 concentration in SF of RA patients was positively correlated with DAS28. Thus, APE1/Ref-1 may reflect the joint inflammation and be associated with disease activity in RA.

scholarly journals Arthritis and the role of endogenous glucocorticoids

Bone Research ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Eugenie Macfarlane ◽  
Markus J. Seibel ◽  
Hong Zhou
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Current Evidence ◽  
Inflammatory Microenvironment ◽  
Glucocorticoid Signaling ◽  
Anti Inflammatory ◽  
Fibroblast Like Synoviocytes

Abstract Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.

Rheumatoid Arthritis and Fibromyalgia: A Frequent Unrelated Association Complicating Disease Management

2009 ◽  
Vol 36 (1) ◽  
pp. 58-62 ◽  
Author(s):  
FABIENNE COURY ◽  
ARNAUD ROSSAT ◽  
ALEXANDRE TEBIB ◽  
MARIE-CLAUDE LETROUBLON ◽  
ANNE GAGNARD ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Joint Destruction ◽  
Constant Factor ◽  
Joint Disease ◽  
Psychosocial Characteristics ◽  
Inappropriate Treatment ◽  
The Relationship ◽  
Worse Prognosis

ObjectiveTo assess the value of the 28-joint Disease Activity Score (DAS28) in evaluating disease activity in rheumatoid arthritis (RA) associated with fibromyalgia (FM). In this situation, because of the weight of the subjective measures included in the DAS28 equation, the patient’s status may be overestimated, leading to inappropriate treatment. We analyze the relationship between RA and FM and discuss whether the association is random or a marker of poor prognosis.MethodsA questionnaire, developed when biologic therapies were introduced, was administered and the results analyzed in a consecutive, female outpatient population including 105 patients with RA, 49 with RA and FM (RAF), and 28 with FM. Psychosocial characteristics, disease presentation, and radiographic joint destruction evaluation were compared in the 3 populations.ResultsThe presentation of RA was the same in patients with RA and RAF, but the 2 populations differed by socioprofessional characteristics, significantly higher disease activity in patients with RAF, and significantly more severe joint destruction in patients with RA. The RAF group was similar to the FM control population in socioprofessional and some physical characteristics. Regression analysis using the DAS28 measures differed significantly in the weight allowed to 28-joint counts for pain and swelling, but the constant factor was higher in patients with RAF.ConclusionDAS28 overestimated objective RA severity in patients who also had FM. The association between RA and FM does not appear to be a marker of worse prognosis, but rather a fortuitous association between the 2 diseases and one that may afford these patients some protection against joint destruction.

Comparison of the Therapeutic Effects of Gold Nanoclusters and Gold Nanoparticles on Rheumatoid Arthritis

2019 ◽  
Vol 15 (11) ◽  
pp. 2281-2290 ◽  
Author(s):  
Yao Zhao ◽  
Zhesheng He ◽  
Ruoping Wang ◽  
Pengju Cai ◽  
Xiangchun Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Au Nanoparticles ◽  
Type Ii Collagen ◽  
Therapeutic Effects ◽  
Type Ii ◽  
Au Clusters ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and progressive cartilage and bone damage. In our previous studies, we found that Au clusters using glutathione as a template (GACs) produced profound anti-inflammatory effects in vitro on lipopolysaccharide (LPS)-induced inflammation in mouse macrophage RAW 264.7 cells and type II collagen-induced rat RA in vivo. In this study, we examined whether the template for Au clusters synthesis has an effect on its anti-inflammatory effect and whether Au nanoparticles with larger particle diameter produce the same anti-inflammatory effect. We synthesized Au clusters with bovine serum albumin (BSA) as a template (BACs), Au clusters with glutathione (GSH) as a template (GACs), and Au nanoparticles with glutathione as a template (GANs) and compared their anti-inflammatory effects in vitro and in vivo. These three Au nanomaterials can inhibit the production of lipopolysaccharide (LPS)-induced proinflammatory mediators and ameliorate type II collagen-induced rat RA. However, although the three Au nanomaterials produced similar anti-inflammatory effects, the GANs with larger particle sizes were less stable in vivo and accumulated in the peritoneum after intraperitoneal injection, resulting in poor absorption in vivo. The BACs showed relatively high liver accumulation due to the larger molecular weight of the outer shell. Therefore, we believe that the GACs are potential reliable nanodrugs for the treatment of RA.

scholarly journals Efficacy of Mitochondrial Antioxidant Plastoquinonyl-decyl-triphenylphosphonium Bromide (SkQ1) in the Rat Model of Autoimmune Arthritis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Alexander A. Andreev-Andrievskiy ◽  
Nataliya G. Kolosova ◽  
Natalia A. Stefanova ◽  
Maxim V. Lovat ◽  
Maxim V. Egorov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Wistar Rats ◽  
Clinical Signs ◽  
Therapeutic Window ◽  
Autoimmune Arthritis ◽  
Dependent Manner ◽  
Specific Pathogen ◽  
Triphenylphosphonium Bromide

Rheumatoid arthritis is one of the most common autoimmune diseases. Many antioxidants have been tested in arthritis, but their efficacy was, at best, marginal. In this study, a novel mitochondria-targeted antioxidant, plastoquinonyl-decyl-triphenylphosphonium bromide (SkQ1), was testedin vivoto prevent and cure experimental autoimmune arthritis. In conventional Wistar rats, SkQ1 completely prevented the development of clinical signs of arthritis if administered with food before induction. Further, SkQ1 significantly reduced the fraction of animals that developed clinical signs of arthritis and severity of pathological lesions if administration began immediately after induction of arthritis or at the onset of first symptoms (day 14 after induction). In specific pathogen-free Wistar rats, SkQ1 administered via gavage after induction of arthritis did not reduce the fraction of animals with arthritis but decreased the severity of lesions upon pathology examination in a dose-dependent manner. Efficacious doses of SkQ1 were in the range of 0.25–1.25 nmol/kg/day (0.13–0.7 μg/kg/day), which is much lower than doses commonly used for conventional antioxidants. SkQ1 promoted apoptosis of neutrophilsin vitro, which may be one of the mechanisms underlying its pharmacological activity. Considering its low toxicity and the wide therapeutic window, SkQ1 may be a valuable additional therapy for rheumatoid arthritis.

scholarly journals Apoptosis of Rheumatoid Arthritis Fibroblast-Like Synoviocytes: Possible Roles of Nitric Oxide and the Thioredoxin 1

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Huili Li ◽  
Ajun Wan
Keyword(s):  
Rheumatoid Arthritis ◽  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Redox System ◽  
Chronic Inflammatory Disease ◽  
Thioredoxin 1 ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. The impaired apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is pivotal in this process. However, the molecular mechanisms responsible for the reduced apoptosis are not fully understood. Both nitric oxide and thioredoxin 1 as two important mediators are widely investigated in the pathogenesis of rheumatoid arthritis. Interestingly, studies have showed that thioredoxin 1 may serve as a master regulator of S-nitrosylation of caspase-3 to fine-tune apoptosisin vivo. Thus, it is anticipated that further investigations on the role of thioredoxin 1 in the S-nitrosylation and denitrosylation of caspase-3 in RA-FLS will likely provide a novel understanding of mechanisms implicated in the impaired apoptosis of RA-FLS. In this paper, we will provide an overview on pathways involved in the reduced apoptosis of RA-FLS and then discuss specially the possible roles of nitric oxide and the thioredoxin 1 redox system associated with apoptosis of RA-FLS.

Correlation of Radiographic Progression with the Cumulative Activity of Synovitis Estimated by Power Doppler Ultrasound in Rheumatoid Arthritis: Difference Between Patients Treated with Methotrexate and Those Treated with Biological Agents

2013 ◽  
Vol 40 (12) ◽  
pp. 1967-1976 ◽  
Author(s):  
Kei Ikeda ◽  
Daiki Nakagomi ◽  
Yoshie Sanayama ◽  
Mieko Yamagata ◽  
Ayako Okubo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Clinical Laboratory ◽  
Joint Destruction ◽  
Power Doppler ◽  
Joint Disease ◽  
Reactive Protein ◽  
Tnf Antagonists ◽  
The Difference ◽  
Modified Total Sharp Score

Objective.Our prospective study aimed to demonstrate that the cumulative synovial power Doppler (PD) ultrasound scores correlate with radiographic progression better than conventional measures in patients with rheumatoid arthritis (RA). We also investigated the difference between antirheumatic agents.Methods.Sixty-nine patients with RA who had recently received either methotrexate (MTX; n = 23), tumor necrosis factor (TNF) antagonists (n = 28), or tocilizumab (TCZ; n = 18) were enrolled. Patients underwent clinical, laboratory, and ultrasonographic assessment at baseline, 12 weeks, and 24 weeks. Radiographic damage was evaluated using van der Heijde modified total Sharp score (TSS) at baseline and 24 weeks.Results.Fifty-seven patients continued the same treatment regimen for 24 weeks and completed the study, and 21 patients (36.8%) showed radiographic progression during the study period. In all patients, ΔTSS significantly correlated both with cumulative 28-joint Disease Activity Score–C-reactive protein (DAS28-CRP; ρ = 0.342, p = 0.009) and cumulative total PD scores (ρ = 0.357, p = 0.006). In MTX-treated patients, cumulative total PD scores significantly correlated with ΔTSS (ρ = 0.679, p = 0.004), whereas cumulative DAS28-CRP did not (ρ = 0.487, p = 0.056). However, cumulative total PD scores did not correlate with ΔTSS in TNF antagonist–treated or TCZ-treated patients.Conclusion.Our data confirm the evidence that synovial PD activity more accurately reflects active synovial inflammation (which actually causes joint destruction) than do conventional measures in patients treated with MTX. Our data also indicate that TNF antagonists can inhibit short-term radiographic progression in the presence of active synovitis.

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