Pathophysiology of Rheumatoid Arthritis

Pathophysiology of rheumatoid arthritis has not yet been completely known. A theory says that in individuals, who are genetically vulnerable to rheumatoid arthritis, some external element like an infection or a trauma can stimulate the autoimmune reaction and can give rise to synovial (the thin lining of the joints) hypertrophy (cell proliferation) and chronic joint inflammation, along with high chances for extra-articular manifestations. Overgrowth of synovial cells and activation of endothelial cells are the early indicators of the pathologic phenomenon that progresses towards uncontrolled inflammation, which consequently gives rise to cartilage and bone damage. The disease is more propagated because of abnormalities in the immune system as well as genetic factors.

Cells that play major role in the pathophysiology of the disease are CD4 T cells, fibroblasts, mononuclear phagocytes and osteoclasts. On the other hand, other cells like B lymphocytes give rise to autoantibodies, i.e. rheumatoid factors (RFs).

The pathogenesis of RA is a complex phenomenon and includes synovial cell proliferation, fibrosis, pannus formation and bone and cartilage erosion.

RA patients show abnormal production of certain inflammatory mediators. These are cytokines and chemokines of numerous types, tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, IL-8, transforming growth factor beta (TGF-beta), fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF).

Inflammation and abundant proliferation of synovium gives rise to destruction of several tissues, which include cartilage, tendons, bones, blood vessels and ligaments. Although the major sites of inflammation and damage are the articular structures, other tissues are severely affected.

The pathophysiology of rheumatoid arthritis is mediated by an inter-related network of cytokines, proteolytic enzymes and prostanoids. IL-1, TNF-alpha, etc. are proinflammatory cytokines and are the central mediators in the disease. This is better seen in rheumatoid arthritis patients, who experience a primary cell-mediated response that results into the raised levels of IL-1 in the synovial fluid.

Further observation is IL-1 concentration in plasma is correlated with the activity of rheumatoid arthritis. It is also observed that patients having erosive rheumatoid arthritis have elevated synovial and circulating levels of IL-1 than patients without erosive activities of the disease.

IL-1 is a notoriously significant cytokine, which has a wide range of activities within the affected joint and are believed to play a major role in causing painful inflammatory signs and symptoms of rheumatoid arthritis. It is a key mediator of pannus formation and synovial inflammation. It is also believed to be a contributor to the hampering of tissue repair processes and the damage to bone and cartilage in rheumatoid arthritis.

Both IL-1 and TNF-alpha have been found to share many biological actions, such as increasing the production of inflammatory mediators like cyclo-oxygenase 2 or COX 2, prostaglandin E2 or PGE2 as well as nitric oxide.

Interleukin (IL)-1 is highly responsible for the signs and symptoms of rheumatoid arthritis. First it mediates inflammation by recruiting neutrophils into the joint, activating macrophages, and stimulating T- and B-cell proliferation and differentiation. Synoviocytes, on their exposure to IL-1, proliferate and produce IL-6, PGE-2 and matrix metalloproteases (MMPs).

Further this production of MMPs causes proteoglycan degradation, which ultimately results into cartilage destruction.

Pathophysiology of rheumatoid arthritis is thus quite complicated, which involves many chemicals, which work interdependently towards bone and cartilage destruction.