A prominent feature of the rheumatoid synovium is the dysregulated hyperplasia of SFs due to a postulated imbalance between growth and apoptosis signals. Stimulation of SFs from RA patients with TNF-a results in enzyme secretion, which may contribute to articular destruction. Induction of apoptosis of this fibroblast population may represent a potential therapeutic approach in RA. Stimulation of cells by TNF-a can generate two signals: one initiates apoptosis, whereas the second leads to activation of NF-?B (which in turn produces inhibitors of apoptosis [IAPs] and promotes the production of pro-inflammatory factors). To induce an apoptotic response in RASFs to TNF-a through adenoviral expression of a truncated stable form of I?Ba and expression of an antisense fragment to XIAP.