Presentation: The Adipokine Visfatin and its Influence on the Inflammatory State in Rheumatoid Arthrits (2007)

147 The Adipokine Visfatin and its Influence on the Inflammatory State in Rheumatoid Arthrits

Objective: Influencing a variety of processes including metabolism, atherosclerosis and inflammation multifunctional adipokines such as adiponectin became a subject of major interest. Visfatin, a recently discovered adipokine, is inducible via trans-signaling through IL-6 in synovial fibroblasts (SF) of patients suffering rheumatoid arthritis (RA). Further cellular lifespan is extended by the enzymatic function of visfatin as nicotinamide phosphoribosyltransferase. Hence, we investigated whether visfatin plays a role in the pathogenesis of RA specifically in joint destruction and contribution to the inflammatory process.
Methods: Visfatin concentrations in synovial fluid of RA, osteoarthritis (OA) and psoriatic arthritis patients were detected by ELISA and correlations to BMI, CRP and ESR were determined. Visfatin expression and localization was determined in RA and OA synovial tissues by immunhistochemistry. Isolation and cell culture of RASF and OASF was performed using standard protocols. RASF and OASF were stimulated with different concentrations of visfatin (between 2.5 to 10000 ng/ml) using adiponectin (25 μg/ml) as positive control. Supernatants were used to perform a cytokine and chemokine antibody array. Afterwards they were investigated by ELISA measuring the production of cytokines and matrix remodelling enzymes (IL-1beta, TNF-alpha, IL-6, IL-8, pro-MMP-1, MMP-3, activin A, follistatin, MCP-1, TIMP-1, TIMP-2).
Results: Visfatin was correlated positively to CRP, but not to ESR or BMI. The mean concentration of visfatin in RA synovial fluid was 77.1 ng/ml. Visfatin was predominantly expressed in the lining layer, lymphoid aggregates and in endothelial cells of capillaries. Furthermore, visfatin induced in a dose-dependent manner the synthesis of IL-6, IL-8, pro-MMP-1, MMP-3 and activin a in RASF. Interestingly, a strong induction of IL-6, IL-8, activin A, MCP-1, MMP-3 and pro-MMP-1 in RASF (6.1-, 51.3-, 1.4-, 3.3-, 3.6-, 1.2-fold) and OASF (6.3-, 56.3-, 2.2-, 3.3-, 6.4-, 2.2-fold) was measured when using physiological visfatin concentrations.
Conclusions: In comparison to adiponectin, visfatin appears to be more prominently expressed in inflamed arthritic tissue. As visfatin exerted also strong stimulatory effects on proinflammatory and matrix-degrading enzymes, the data support the idea that visfatin is a highly potent molecule in the pathophysiology of RA.

 F.M. Meier, None.