Induction of immune tolerance in the treatment of rheumatoid arthritis.

Progress in our understanding of the genetics and immunology of rheumatoid arthritis (RA) has translated into clinical practice with the introduction of a first generation of biologic agents that effectively interfere with the inflammatory cascade by blocking a key component. This evolution has not only changed the way we practice, but perhaps also the way we think about RA and its treatment. In our view direct manipulation of specific pathogenic pathways is increasingly being used to replace generalized pharmacological immune suppression. The next leap forward will be to develop therapeutic approaches that will lead to maintenance of disease remission with a minimal-treatment or even drug-free regimen, relying on the induction of immune tolerance rather than the suppression of the immune system. Immune tolerance has the potential to prevent tissue damage secondary to inflammatory responses while at the same time maintaining homeostasis through physiologic recognition of self and the ability to perceive and react to 'danger'. Novel therapeutic approaches are emerging from these concepts. Such therapies will hopefully be safe and efficacious, and will complement the first generation of biologic agents that are currently available.