Signal transduction pathways – future targets of treatment in rheumatoid arthritis?

Overview

Understanding of the role of cytokine network in inflammation has led to development of novel biological agents which have been of the major breakthrough in the therapy of rheumatoid arthritis during the last few years. More than half of the patients in clinical trials do not achieve ACR50 responses and remissions are still rare. Anti-cytokine drugs could also have serious side effects. Therefore significant efforts are focused on characterizing the signal transduction cascades that are activated by these cytokines and, in turn, regulate their expression. The most light is shed on the mitogen activated protein-kinase (MAPK), JAK/STAT and transcription factor NF-κB cascades that are pivotal regulators of expression of proinflammatory mediators. Active forms of these proteinkinases and transcription factors are expressed in rheumatic joint tissue and their proper inhibitors should provide novel therapeutic intervention in rheumatoid arthritis in the near future.

Key words:
rheumatoid arthritis, signal transduction cascade, mitogen activated protein-kinase (MAPK), JAK/STAT, transcription factor NF-κB