Activation of TLR8 on monocytes and myeloid dendritic cells triggers an inflammatory response associated with tumor necrosis factor-α (TNFα) production and modulates the adaptive cellular immune response via the production of interleukin-12 (IL-12). Recently, TLR8 expression and function has been implicated in various human autoimmune diseases including rheumatoid arthritis (Sacre S, et al. J of Immun 2008; 181:8002–8009) and inflammatory bowel disease (Saruta M, et al. Inflamm Bowel Dis 2009; 15:321–327).

VentiRx is developing small molecule antagonists that inhibit responses to TLR8. VTX-763 is a preclinical lead which shows marked inhibition of TNFα production in vitro, and inhibits TLR8-induced NF-kB activation.