scholarly journals Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 827 ◽  
Author(s):  
Roxana Coras ◽  
Jessica Murillo-Saich ◽  
Monica Guma
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiome ◽  
Potential Role ◽  
Joint Destruction ◽  
Systemic Autoimmune Disease ◽  
Loss Of Function ◽  
Dietary Interventions ◽  
Rheumatoid Arthritis Pathogenesis ◽  
Therapeutic Drugs ◽  
Anti Inflammatory

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved the treatment of RA, patients often inquire about dietary interventions to improve RA symptoms, as they perceive pain and/or swelling after the consumption or avoidance of certain foods. There is evidence that some foods have pro- or anti-inflammatory effects mediated by diet-related metabolites. In addition, recent literature has shown a link between diet-related metabolites and microbiome changes, since the gut microbiome is involved in the metabolism of some dietary ingredients. But diet and the gut microbiome are not the only factors linked to circulating pro- and anti-inflammatory metabolites. Other factors including smoking, associated comorbidities, and therapeutic drugs might also modify the circulating metabolomic profile and play a role in RA pathogenesis. This article summarizes what is known about circulating pro- and anti-inflammatory metabolites in RA. It also emphasizes factors that might be involved in their circulating concentrations and diet-related metabolites with a beneficial effect in RA.

scholarly journals Pharmacomicrobiology of Methotrexate in Rheumatoid Arthritis: Gut Microbiome as Predictor of Therapeutic Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Huanhuan Yan ◽  
Ru Sui ◽  
Hongwei Xue ◽  
Chong Gao ◽  
Xiaofeng Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Precision Medicine ◽  
Gut Microbiome ◽  
Clinical Status ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Bacterial Strains ◽  
Joint Deformity ◽  
Subsequent Response ◽  
Anti Inflammatory

Rheumatoid arthritis (RA) is a disabling autoimmune disease with invasive arthritis as the main manifestation and synovitis as the basic pathological change, which can cause progressive destruction of articular cartilage and bone, ultimately leading to joint deformity and loss of function. Since its introduction in the 1980s and its widespread use in the treatment of RA, low-dose methotrexate (MTX) therapy has dramatically changed the course and outcome of RA treatment. The clinical use of this drug will be more rational with a better understanding of the pharmacology, anti-inflammatory mechanisms of action and adverse reaction about it. At present, the current clinical status of newly diagnosed RA is that MTX is initiated first regardless of the patients’ suitability. But up to 50% of patients could not reach adequate clinical efficacy or have severe adverse events. Prior to drug initiation, a prognostic tool for treatment response is lacking, which is thought to be the most important cause of the situation. A growing body of studies have shown that differences in microbial metagenomes (including bacterial strains, genes, enzymes, proteins and/or metabolites) in the gastrointestinal tract of RA patients may at least partially determine their bioavailability and/or subsequent response to MTX. Based on this, some researchers established a random forest model to predict whether different RA patients (with different gut microbiome) would respond to MTX. Of course, MTX, in turn, alters the gut microbiome in a dose-dependent manner. The interaction between drugs and microorganisms is called pharmacomicrobiology. Then, the concept of precision medicine has been raised. In this view, we summarize the characteristics and anti-inflammatory mechanisms of MTX and highlight the interaction between gut microbiome and MTX aiming to find the optimal treatment for patients according to individual differences and discuss the application and prospect of precision medicine.

scholarly journals Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview

2021 ◽  
Vol 10 (6) ◽  
pp. 1241
Author(s):  
Yoshiya Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Kinase Inhibitors ◽  
Joint Destruction ◽  
Joint Damage ◽  
Nuclear Factor Κb ◽  
Cartilage Destruction ◽  
Janus Kinase ◽  
Systemic Autoimmune Disease ◽  
And Cartilage

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.

Rheumatoid arthritis—clinical features

2013 ◽  
Author(s):  
Eugen Feist ◽  
Gerd-R. Burmester
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Features ◽  
Clinical Laboratory ◽  
Systemic Disease ◽  
Systemic Autoimmune Disease ◽  
Joint Involvement ◽  
Loss Of Function ◽  
Increased Risk ◽  
Autoantibody Status ◽  
Disease Entities

Rheumatoid arthritis (RA) presents with variable clinical features, making this most frequent chronic systemic autoimmune disease with characteristic joint involvement a diagnostic and therapeutic challenge. This chapter describes in detail the different clinical, laboratory and imaging findings in patients with RA. In addition to the characteristic arthritic involvement, which can lead to severe joint changes with progressive destruction and loss of function, other systemic disease manifestations as well as an increased risk for cardiovascular events and non-Hodgkin's lymphoma with relevance for patients' prognosis are described. Recent approaches to early diagnosis and stratification of patients by predictive factors for a severe course of disease are discussed. These patient profiles include increased inflammatory markers, the presence of autoantibodies, and erosive changes at the time of diagnosis. The novel classification criteria for RA and the significance of autoantibody status, namely seropositivity for antibodies against citrullinated antigens as highly specific diagnostic markers, are highlighted to further promote early differentiation of RA from other arthritic disease entities.

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.

scholarly journals Current Therapeutic Options in the Treatment of Rheumatoid Arthritis

2019 ◽  
Vol 8 (7) ◽  
pp. 938 ◽  
Author(s):  
Köhler ◽  
Günther ◽  
Kaudewitz ◽  
Lorenz
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Disease Activity ◽  
Physical Function ◽  
Chronic Inflammation ◽  
Early Treatment ◽  
Joint Destruction ◽  
Therapeutic Options ◽  
Systemic Autoimmune Disease ◽  
Control Disease

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints. Untreated RA leads to a destruction of joints through the erosion of cartilage and bone. The loss of physical function is the consequence. Early treatment is important to control disease activity and to prevent joint destruction. Nowadays, different classes of drugs with different modes of action are available to control the inflammation and to achieve remission. In this review, we want to discuss differences and similarities of these different drugs.

Potential role of bioactive lipids in rheumatoid arthritis

2021 ◽  
Vol 27 ◽  
Author(s):  
Wheeler Torres ◽  
Mervin Chávez-Castillo ◽  
José L. Peréz-Vicuña ◽  
Rubén Carrasquero ◽  
María P. Díaz ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Potential Role ◽  
The Body ◽  
Omega 3 ◽  
Bioactive Lipids ◽  
Dietary Interventions ◽  
Complex Disorder ◽  
Inflammatory Autoimmune Disease

: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which involves a pathological inflammatory response against articular cartilage in multiple joints throughout the body. It is a complex disorder associated with comorbidities such as depression, lymphoma, osteoporosis and cardiovascular disease (CVD), which significantly deteriorate patients’ quality of life and prognosis. This has ignited a large initiative to elucidate the physiopathology of RA, aiming to identify new therapeutic targets and approaches in its multidisciplinary management. Recently, various lipid bioactive products have been proposed to have an essential role in this process; including eicosanoids, specialized pro-resolving mediators, phospholipids/sphingolipids, and endocannabinoids. Dietary interventions using omega-3 polyunsaturated fatty acids or treatment with synthetic endocannabinoids agonists have been shown to significantly ameliorate RA symptoms. Indeed, the modulation of lipid metabolism may be crucial in the pathophysiology and treatment of autoimmune diseases.

scholarly journals Identification of small molecule inhibitors of RANKL and TNF signalling as anti-inflammatory and antiresorptive agents in mice

2013 ◽  
Vol 74 (1) ◽  
pp. 220-226 ◽  
Author(s):  
Emmanuel Coste ◽  
Iain R Greig ◽  
Patrick Mollat ◽  
Lorraine Rose ◽  
Mohini Gray ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Loss ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Joint Destruction ◽  
Luciferase Reporter ◽  
Collagen Induced Arthritis ◽  
Arthritis Model ◽  
Anti Inflammatory ◽  
Systemic Bone Loss

IntroductionInflammatory joint diseases such as rheumatoid arthritis are associated with local bone erosions and systemic bone loss, mediated by increased osteoclastic activity. The receptor activator of nuclear factor (NF) κB ligand (RANKL) plays a key role in mediating inflammation-induced bone loss, whereas tumour necrosis factor (TNF) plays a central role in the inflammatory process. Here we tested whether a recently identified class of small molecule inhibitors of RANKL signalling (ABD compounds) also affect TNF signalling and whether these compounds inhibit inflammation in an animal model of rheumatoid arthritis.MethodsThe inhibitory effects of the ABD compounds on TNF-induced signalling were tested in mouse macrophage cultures by western blotting and in an NFκB luciferase-reporter cell line. The anti-inflammatory effects of the compounds were tested in the mouse collagen-induced arthritis model of rheumatoid arthritis.ResultsThe ABD compounds ABD328 and ABD345 both inhibited TNF-induced activation of the NFκB pathway and the extracellular signal-regulated kinase (ERK) and Jun kinase (JNK) mitogen activated protein kinases (MAPKs). When tested in the mouse collagen-induced arthritis model of rheumatoid arthritis, the compounds suppressed inflammatory arthritis, inhibited joint destruction and prevented systemic bone loss. Furthermore, one of the compounds (ABD328) showed oral activity.ConclusionsHere we describe a novel class of small molecule compounds that inhibit both RANKL- and TNF-induced NFκB and MAPK signalling in osteoclasts and macrophages, and inflammation and bone destruction in a mouse model of rheumatoid arthritis. These novel compounds therefore represent a promising new class of treatments for inflammatory diseases, such as rheumatoid arthritis.

scholarly journals HBEGF+ macrophages identified in rheumatoid arthritis promote joint tissue invasiveness and are reshaped differentially by medications

2019 ◽  
Author(s):  
David Kuo ◽  
Jennifer Ding ◽  
Ian Cohn ◽  
Fan Zhang ◽  
Kevin Wei ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Egf Receptor ◽  
Wide Spectrum ◽  
Joint Destruction ◽  
Human Macrophage ◽  
Dependent Manner ◽  
Human Tissues ◽  
Joint Tissue ◽  
Macrophage Phenotypes ◽  
Anti Inflammatory

AbstractMacrophages tailor their function to the signals found in tissue microenvironments, taking on a wide spectrum of phenotypes. In human tissues, a detailed understanding of macrophage phenotypes is limited. Using single-cell RNA-sequencing, we define distinct macrophage subsets in the joints of patients with the autoimmune disease rheumatoid arthritis (RA), which affects ~1% of the population. The subset we refer to as HBEGF+ inflammatory macrophages is enriched in RA tissues and shaped by resident fibroblasts and the cytokine TNF. These macrophages promote fibroblast invasiveness in an EGF receptor dependent manner, indicating that inflammatory intercellular crosstalk reshapes both cell types and contributes to fibroblast-mediated joint destruction. In an ex vivo tissue assay, the HBEGF+ inflammatory macrophage is targeted by several anti-inflammatory RA medications, however, COX inhibition redirects it towards a different inflammatory phenotype that is also expected to perpetuate pathology. These data highlight advances in understanding the pathophysiology and drug mechanisms in chronic inflammatory disorders can be achieved by focusing on macrophage phenotypes in the context of complex interactions in human tissues.One Sentence SummaryA newly identified human macrophage phenotype from patients with the autoimmune condition RA is found to promote joint tissue invasiveness and demonstrates variable sensitivities to anti-inflammatory medications used to treat the disease.

scholarly journals ROLE OF PANCHAKARMA IN MANAGEMENT OF RHEUMATOID ARTHRITIS

2021 ◽  
Vol 9 (04) ◽  
pp. 122-126
Author(s):  
Panchola Priyanka ◽  
◽  
Joshi Neha ◽  
Deepshikha a ◽  
Garg G.P ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Systemic Disease ◽  
Modern Science ◽  
Body Part ◽  
The Body ◽  
Systemic Autoimmune Disease ◽  
Loss Of Function ◽  
Abnormal Immune Response

Rheumatoid arthritis is a systemic autoimmune disease that causes chronic inflammation of the joints.It causes inflammation of the tissue around the joints. As the disease advancement, the inflamed synovium occupies and damages the cartilage and bone of the joint. An autoimmune disease is a condition characterized by an abnormal immune response to a normal body part. Because it can affect various organs of the body, rheumatoid arthritis is referred to as a systemic disease and ultimately called rheumatoid disease. In Ayurvedaamavata is correlated with rheumatoid arthritis. Vitiatedvata and ama plays major role in the manifestation of amavata. Improper digestion of Rasaadidhatu leads to the formation of ama. Vitiated ama leads swelling, pain, stiffness, in many joints along with loss of function. Modern science does not offer any cure of RA, the management aims are limited. This article reviews the line of treatment for the management of amavata described by Acharyachakradatta. It was concluded that rheumatoid arthritis can be completely cured or treated with Ayurveda medication and Panchakarma therapies without any side effects.

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