Figure 1. Proposed model of Eritoran-mediated protection in influenza infection. Oxidized phospholipids, produced in response to viral infection, are proposed to bind to CD14 before being transferred to lymphocyte antigen 96
(LY96; MD2). The lipid-MD2 complex interacts with toll-like receptor 4 (TLR4), resulting in receptor dimerization and activation.

Intracellular adaptor proteins-toll-interleukin 1 receptor domain containing adaptor protein (TIRAP), toll-like receptor adaptor molecule 2 (TICAM2; TRAM), myeloid differentiation primary response gene 88 (MYD88) and TICAM1 (TRIF)-are then recruited, and the signal is transmitted inside the cell. TLR4 signaling that occurs through MYD88 activates NF-kB to induce production of proinflammatory cytokines, whereas TLR4 signaling that occurs through TRIF activates interferon regulatory factor 3 (IRF3) to induce production of type I interferons.

Points in the signaling pathway at which Eritoran may block influenza virus-induced inflammation are indicated in red.

Vogel's group speculates that Eritoran can inhibit interactions of oxidized phospholipids with either CD14 or MD2, thus diminishing TLR4 signaling and production of cytokines. This would blunt the effect of cytokines on reactive oxygen species (ROS) generation and therefore limit the production of oxidized phospholipids. (Figure based on Figure 8 in ref. 1.)