Structural-functional relationships of TNF-alpha antagonists: next steps

The balance between effective tumor necrosis factor (TNF) blockade to control aggressive autoimmune disease states and adequate remaining TNF activity to confer immunoprotection against infections such as tuberculosis is an important and complex issue. An increased scientific understanding of how each of the TNF antagonist agents affects the complex interactions of the inflammation cascade and apoptosis, and whether the effects are modulatory or destructive, is needed. The data presented in this supplement highlight the need for further research into these key areas, and illustrate our current understanding of the mode of action of TNF blockers as only the tip of the iceberg.