Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation causing progressive joint damage that can lead to lifelong disability. The pathogenesis of RA involves a complex network of various cytokines and cells that trigger synovial cell proliferation and cause damage to both cartilage and bone. Involvement of the cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 is central to the pathogenesis of RA, but recent research has revealed that other cytokines such as IL-7, IL-17, IL-21, IL-23, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-18, IL-33, and IL-2 also play a role. Clarification of RA pathology has led to the development of therapeutic agents such as biological disease-modifying anti-rheumatic drugs (DMARDs) and Janus kinase (JAK) inhibitors, and further details of the immunological background to RA are emerging. This review covers existing knowledge regarding the roles of cytokines, related immune cells and the immune system in RA, manipulation of which may offer the potential for even safer and more effective treatments in the future.

Diagnostic Value of Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte, and Monocyte-to-Lymphocyte Ratios for the Assessment of Rheumatoid Arthritis in Patients with Undifferentiated Inflammatory Arthritis

“…Neutrophils, platelets, monocytes/macrophages, and lymphocytes are known to be actively involved in the pathogenesis of RA [ 30 , 31 , 32 , 33 , 34 , 35 ]. Monocytes circulate in the bloodstream and migrate into the inflamed synovium, where they can differentiate into macrophages.…”

“…RF and anti-citrullinated protein antibodies (ACPA) in RA patients can form immune complexes with citrullinated proteins in the synovium and subsequently activate synovial macrophages, resulting in the production of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6, which are the central processes in the pathogenesis of RA [ 33 ]. Activated macrophages activate fibroblast-like synoviocytes (FLS) to promote the secretion of pathogenic mediators, including matrix metalloproteinase and granulocyte macrophage colony-stimulating factors, which cause bone erosion in RA [ 33 ]. Neutrophils are the most abundant type of white blood cells and are responsible for the first cellular response to acute inflammation or injury.…”

CD8+ T Cell Senescence: Lights and Shadows in Viral Infections, Autoimmune Disorders and Cancer

“…The chronic inflammation observed in several autoimmune diseases may also overlap with the low-grade inflammation found in elderly people [ 62 ]. In particular, IL-6, a pro-inflammatory cytokine implicated in the cytokine storm occurring in severe COVID-19, is upregulated in both inflammaging and Rheumatoid Arthritis (RA), a chronic autoimmune rheumatic disease [ 62 , 63 , 64 , 65 , 66 ]. In addition, the cartilage tissue-invasive CD4 + T cells from patients with RA showed a significant telomere frailty, a senescence hallmark, due to a low expression of the double-strand-break repair nuclease Meiotic Recombination 11 Homolog A (MRE11A) [ 67 ].…”

Effects of nonsurgical periodontal therapy in patients with rheumatoid arthritis: a prospective before and after study

“…The etiology of RA is unknown but genetic, environmental factors and smoking have been recognized as significant risk factors, and more recently, dysbiosis of the gut microbiome has been associated as a contributing factor for autoimmune diseases including RA [11][12][13] . In addition, RA affects the joints and contributes to chronic systemic inflammation and, therefore, compromises multiple organs and tissues in the body 14 .…”

“…La etiología de la AR se desconoce, pero los factores genéticos, ambientales y el tabaquismo se han reconocido como factores de riesgo importantes y, más recientemente, la disbiosis del microbioma intestinal se ha asociado como un factor que contribuye a enfermedades autoinmunes, incluida la AR 11 - 13 . Además, la AR afecta las articulaciones y contribuye a la inflamación sistémica crónica y, por tanto, compromete múltiples órganos y tejidos del cuerpo 14 .…”