| Popis: |
In rheumatoid arthritis (RA), synovial membrane exhibits features suggesting that components of innate and acquired immune responses are of functional importance. In particular, the role of both T cell dependent and independent mechanisms in promoting cytokine networks has received much attention [1]. Cytokines mediate a wide variety of immunological actions and are key mediators in the pathogenesis of human autoimmune disease. Their pleiotropic functions and propensity for synergistic interactions and functional redundancy render them intriguing therapeutic targets. Thus far, single cytokine targeting has proven useful in several rheumatic diseases states. Perhaps the clearest evidence for the central role of these molecules in disease is the success of TNFα-blocking therapies. These have elucidated, for the first time, definitive critical checkpoints in proinflammatory cascades. However, non-or partial-responder patients are not infrequent and inflammatory disease usually flares upon discontinuation of treatment [2, 3]. The fact that TNFα independent pathways operate in inflammatory synovitis carries significant pathogenetic implications for existing disease models and exemplifies the clinical necessity for generation of further novel, pathogenesis-lead interventions. |
