scholarly journals Inflammation in the Pathogenesis of Rheumatoid Arthritis and in Experimental Arthritis: Evaluation of Combinations of Carnosic Acid and Extract of Rhodiola rosea L. with Methotrexate

2021 ◽  
Author(s):  
Silvester Ponist ◽  
Katarina Pruzinska ◽  
Katarina Bauerova

The host immune response generates the pro-inflammatory immune response as a protective measure against invading pathogens, allergens, and/or trauma. However, dysregulated and chronic inflammation may result in secondary damage to tissues and immune pathology to the host. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease which primarily involves synovial inflammation, joint pain, immobility, and stiffness. Increased infiltration of inflammatory immune cells and fibroblast-like synoviocytes into joints, form pannus and small blood vessels that lead to synovium and cartilage destruction. In this chapter we will focus on the role of inflammatory cytokines (IL-1β, IL-6 and IL-17), chemokine monocyte chemotactic protein-1 and matrix metalloproteinase-9 in the pathogenesis of experimental arthritis in animals and in human RA. Further, we will be discussing about methotrexate’s (cornerstone of anti-rheumatic therapy) immune suppressing activity, anti-inflammatory properties of carnosic acid and extract of Rhodiola rosea L., and their innovative combination treatments with methotrexate in rat adjuvant arthritis.

2021 ◽  
Vol 10 (6) ◽  
pp. 1241
Author(s):  
Yoshiya Tanaka

In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-κB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.


2022 ◽  
Vol 23 (2) ◽  
pp. 905
Author(s):  
Sunhee Jang ◽  
Eui-Jong Kwon ◽  
Jennifer Jooha Lee

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.


2015 ◽  
Vol 24 (4) ◽  
pp. 189-193
Author(s):  
Ina Cambu ◽  
◽  
Catalina Raluca Nuta ◽  
Denisa Predeteanu ◽  
◽  
...  

Rheumatoid arthritis (RA) is a systemic autoimmune disease, leading to synovial hypertrophy and adjacent bone and cartilage destruction. The combined use of biological agents and methotrexate (MTX) has revolutionised the treatment of RA producing significant improvements in clinical, radiographic and functional outcomes. The results of clinical study and experience of the specialities of rheumatology in clinical statement showed the long treatment may be associated with side effects, in addition biological treatment means high cost. The next goal should be remission without the use of biological agents. That’s why new treatment in RA means the tapering or even stopping the biological treatment in patients with RA who reached remission. In association with the new recommendation EULAR in 2013 there are many studies which showed the possibility of tapering or discontinuing the biological therapy in patients in sustained remission.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Larissa Lumi Watanabe Ishikawa ◽  
Priscila Maria Colavite ◽  
Larissa Camargo da Rosa ◽  
Bianca Balbino ◽  
Thais Graziela Donegá França ◽  
...  

Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. It affects mainly the joints, causing synovitis, cartilage destruction, and bone erosion. Many experimental models are used to study the mechanisms involved in immunopathogenesis and new therapies for this disease. Proteoglycan-induced arthritis (PGIA) is a widely used model based on the cross-reactivity of injected foreign (usually human) PG and mice self-PG. Considering the complexity of the extraction and purification of human PG, in this study we evaluated the arthritogenicity of bovine PG that is commercially available. Bovine PG was highly arthritogenic, triggering 100% incidence of arthritis in female BALB/c retired breeder mice. Animals immunized with bovine PG presented clinical symptoms and histopathological features similar to human RA and other experimental models. Moreover, bovine PG immunization determined higher levels of proinflammatory and anti-inflammatory cytokines in arthritic mice compared to healthy ones. As expected, only the arthritic group produced IgG1 and IgG2a antibodies against PG. Thus, commercial bovine PG can be used as an alternative antigenic source to PGIA for the study of many RA aspects, including the immunopathogenesis of the disease and also the development of new therapies.


2021 ◽  
Vol 22 (5) ◽  
pp. 2426
Author(s):  
Askhat Myngbay ◽  
Limara Manarbek ◽  
Steve Ludbrook ◽  
Jeannette Kunz

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1108.1-1108
Author(s):  
D. Monova ◽  
S. Monov ◽  
R. Shumnalieva ◽  
D. Dimova ◽  
M. Sotirova

Background:Rheumatoid arthritis (RA) is the most common systemic autoimmune disease and is associated with a number of extra-articular organ manifestations, including ocular complications.Objectives:The aim of this study is to evaluate the frequency and characteristics of ocular manifestation in patients with rheumatoid arthritis (RA).Methods:The study involved 87 patients with RA. All the study subjects underwent complete ophthalmological examination involving visual acuity assessment, examination of anterior and posterior eye segments, Schirmer’s test, diameter and mobility of pupils, as well as eyeball mobility assessment of intraocular pressure. Data regarding age, gender, disease duration, age at diagnosis, systemic corticosteroid use, blood pressure, ocular symptoms and detailed ophthalmic history were recorded. The presence of rheumatoid factor in serum was evaluated by standard test methods based on principle of agglutination. All patients were seropositive.Results:87 patients (26 male, 59 female, mean age 45,6 ± 13,1 years; mean disease duration 7,4 ± 6,2 years) with RA were enrolled in this study. 31 (35,63 %) of them had no ocular symptoms. Among the patients with ocular symptoms, 39 (69,64 %) complained of decreased vision, 33 (58,93 %) - of dry eye, 32 (57,14 %) - of burning, 29 (51,78 %) -photophobia, 28 (50 %) - of gritty sensation, 27 (48,21 %) - of itching, 18 (32,14 %) - of redness, 13 (23,21 %) - of ocular pain, 3 (5,36 %) - of floaters. Ophthalmological examination revealed higher incidence of the following abnormalities in the study group: myopic astigmatism - in 10 (5,74 %) eyes, vascular abnormalities within fundus - in 22 (12,64 %) eyes, increased intraocular pressure (> 21 mm Hg) - in 11 (6,32 %) eyes. Mean IOP values were 17,34 ± 5,12 mm Hg. In 48 eyes Schirmer’s test results were below 10 mm, and in 18 eyes - below 5 mm. Keratoconjunctivitis sicca was present in 31 (35,63 %) of all patients. Episcleritis was diagnosed in 4 patients (4,6 %), scleritis – in 3 (3,45 %). Retinal vasculitis was present in 2 (2,3 %) patients and involves veins and arteries peripheral branches. Lens opacity was found in 13 (14,94 %) patients (21 eyes), mostly in the form of posterior subcapsular cataract (in 16 eyes) and nuclear cataract (in 5 eyes). The mean age of patients with cataracts was 52,3 ± 14,2 years. 13 of the patients with cataracts were either currently taking or had previously taken systemic corticosteroids.Conclusion:In patients with RA numerous abnormalities within the vision of organ may be found. Ocular symptoms are relatively common complications of RA, and may result in irreversible changes in the organ of vision. Regular ophthalmological examinations are essential among the patients with RA.Disclosure of Interests:None declared


2013 ◽  
Vol 15 (6) ◽  
Author(s):  
John M Davis ◽  
Keith L Knutson ◽  
Michael A Strausbauch ◽  
Abigail B Green ◽  
Cynthia S Crowson ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina Kurz ◽  
Manfred Herold ◽  
Elisabeth Russe ◽  
Werner Klotz ◽  
Guenter Weiss ◽  
...  

Background. Rheumatoid arthritis is a systemic autoimmune disease characterized by joint erosions, progressive focal bone loss, and chronic inflammation.Methods. 20 female patients with moderate-to-severe rheumatoid arthritis were treated with anti-TNF-antibody adalimumab in addition to concomitant antirheumatic therapies. Patients were assessed for overall disease activity using the DAS28 score, and neopterin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) concentrations as well as osteoprotegerin (OPG) and soluble receptor activator of NF-κB ligand (sRANKL) concentrations were determined before therapy and at week 12. Neopterin as well as OPG and sRANKL were determined by commercial ELISAs.Results. Before anti-TNF therapy patients presented with high disease activity and elevated concentrations of circulating inflammatory markers. OPG concentrations correlated with neopterin (rs=0.494,p=0.027), but not with DAS28. OPG concentrations and disease activity scores declined during anti-TNF-treatment (bothp<0.02). Patients who achieved remission (n=7) or showed a good response according to EULAR criteria (n=13) presented with initially higher baseline OPG levels, which subsequently decreased significantly during treatment (p=0.018for remission,p=0.011for good response).Conclusions. Adalimumab therapy was effective in modifying disease activity and reducing proinflammatory and bone remodelling cascades.


Author(s):  
Domenico Galasso ◽  
Massimo L’Andolina ◽  
Norma M. Marigliano ◽  
Salvatore Galasso ◽  
Giovanni Forte

Rheumatoid arthritis is a systemic autoimmune disease, mainly poli-artycular, among wide-spread chronic inflammatory diseases, that cause pain, functional limitation, damage and joints deformations, and disability. It is characterized by turns of active inflammation and remission phases. Inflammation degree and persistence are associated to a bad functional prognosis and progressive joint disability. These patients management require a continuous valuation of inflammatory activity index of disease both therapeutic management and to prevent disablement process. We focus on many valuation index of joint disability and functional damage. Very important are both the scales of auto-values concerning the pain and the joint swelling and clinical data get by physician to valuate activity index of disease as defined by DAS28. Significant data come by health-related quality of life, disability and by AIMS2 (Arthritis Impact Measurement Scale).


2021 ◽  
Author(s):  
Lisa G.M. van Baarsen ◽  
Tineke A. de Jong ◽  
Maria J.H. de Hair ◽  
Johanna F. Semmelink ◽  
Ivy Y. Choi ◽  
...  

AbstractBackgroundPrevious work has shown subtle infiltration of synovial T cells in the absence of overt synovial inflammation in individuals at risk of developing rheumatoid arthritis (RA).ObjectiveTo study the molecular changes in synovium preceding arthritis development in at risk individuals.Materials and methodsWe included sixty-seven individuals with arthralgia who were IgM rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive and without any evidence of arthritis. All individuals underwent mini-arthroscopic synovial tissue sampling of a knee joint at baseline and were followed prospectively. An explorative genome-wide transcriptional profiling study was performed on synovial tissue using Agilent arrays (discovery cohort). Survival analysis was used to identify transcripts associated with arthritis after follow up. Expression levels of differentially expressed genes were validated using quantitative real-time PCR (qPCR). Immunohistochemistry was used to study gene candidates at the protein level in situ.ResultsIn the discovery cohort, 6 of the 13 at risk individuals developed RA after a median follow-up time of 20 months (IQR 2 – 44; pre-RA). The 7 individuals who did not develop RA had a median follow-up time of 85 months (IQR 69 – 86). Using a False Discovery Rate of <5% we found increased expression of 3,151 transcripts correlating with a higher risk of arthritis development, whereas increased expression of 2,437 transcripts correlated with a lower risk. Gene set enrichment analysis revealed that synovial biopsies of pre-RA individuals display higher expression of genes involved in several immune response-related pathways compared with biopsies of individuals who did not develop RA. In contrast, lower expression was observed for genes involved in extracellular matrix receptor interaction, Wnt-mediated signal transduction and lipid metabolism. Two-way hierarchical cluster analysis of 27 genes measured by qPCR classified the synovial biopsies of 61 individuals into two groups, where pre-RA individuals (n=16) showed a preference to cluster together. Synovial tissue from pre-RA individuals were more likely to show podoplanin positive cells and lower lipid staining compared with synovial tissue from individuals who did not develop RA.ConclusionMolecular changes can be detected in synovial tissues before clinical onset of arthritis. Alterations in the immune response genes and lipid metabolism are associated with development of arthritis.


Sign in / Sign up

Export Citation Format

Share Document