“…Accordingly, our understanding of the TLR-tolerized state (defined only as the inability to make TNF-a upon restimulation with a TLR agonist; Fan and Cook, 2004) is incomplete. The state seems to result from a cell differentiation process mediated by genes whose expression can be blocked by the transcriptional inhibitor, actinomycin D (Shi et al, 2007). The nature of the genes required is not clear, but may include the cytokines IL-10 and TGF-b (as these have been implicated in the endotoxin tolerant state in monocytes; Randow et al, 1995) along with intracellular molecules, such as SOCS1, IL receptor-associated kinase M, MyD88s, ST2 and A20, which have been implicated in negative regulation of TLR signaling (Miggin and O'Neill, 2006).…”