Synovial inflammation

Rheumatoid arthritis (RA) affects 1% of the US population, or 3 million people (1-3). Although women are 2.5 times more likely to get RA than men, some studies suggest the disease tends to be more severe in men. RA can affect people of all ages, but prevalence increases with age, approaching 5% in women over 55 years of age (1-3). RA is a chronic inflammatory disease characterized by synovial inflammation and hyperplasia, neovascularization, and progressive destruction of cartilage and bone (1,4,5). The cause(s) of RA remains poorly... 

Kraan MC, Patel DD, Haringman JJ, et al. The development of clinical signs of rheumatoid synovial inflammation is associated with increased synthesis of the chemokine CXCL8 (interleukin-8). Arthritis Res 2001 3(1) 65-71. 

IL-18 augments T- and NK-cell maturation, cytotoxicity and cytokine production. It stimulates TH differentiation, promotes secretion of TNF-a, IFN-y and GM-CSF and enhances NK cell cytotoxicity by increasing FasL expression. IL-8-mediated neutrophil chemotaxis is promoted by IL-18 via its effects on TNF-a and IFN-y, which are stimulatory in action. It plays an important role in maintaining synovial inflammation and inducing joint destruction in rheumatoid arthritis. In synovium of patients with rheumatoid arthritis, enhanced levels of TNF-a and IL-1 are associated with augmented expression of IL-18. 

In clinical practice, laboratory measures used to monitor those inflammatory diseases are C-reactive protein and erythrocyte sedimentation rate. Recent studies have shown that the use of S100A8/S100A9 proteins as markers of synovial inflammation is even superior to C-reactive protein and erythrocyte sedimentation rate (Kane et al., 2003). 

Sweeney SE, Firestein GS. Rheumatoid arthritis regulation of synovial inflammation./wt / Biochem Cell Biol. 2004 36 372-378. 

Sedgwick, A.D. Lees, P. (1986) Studies of eicosanoid production in the air pouch model of synovial inflammation. Agents and Actions, 18, 429-438. 

Flagg S D, Meador R, Hsia E, et al. (2005). Decreased pain and synovial inflammation after etanercept therapy in patients with reactive and undifferentiated arthritis An open-label trial. Arthrit. Rheumatism. 53 613-617. 

Agalactosyl glycoforms of IgG Rheumatoid arthritis Gal-deficient iV-glycans in serum IgG causing complexation with ManBL that initiates/ perpetuates synovial inflammation. 

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