The cyclic structure of RTD-1 is required for this activity, and the inhibition of ADAM17/TACE is abrogated in the noncyclic isoform of RTD-1.13 Consistent with this anti-TNF effect, RTD-1 was highly effective in rat pristane–induced arthritis,14 a widely used model of rheumatoid arthritis14–16 that is a TNF-driven autoimmune disease. This evidence concerns the gene TNF and autoimmune disease.