A Novel Class of Small Molecule Agonists with Preference for Human over Mouse TLR4 Activation
Fig 11
AZ618 demonstrates in vivo activity in hTLR4/MD2 KIKO mice.
C57BL/6 mice (6–12 per group) were immunized IP with 50 μg MPL or AZ618 and then were bled at 2 h via retro-orbital route and at 6 h via cardiac puncture. Serum was analyzed by multiplex Millipore kits for cytokine content. Presented are individual results with a bar representing the group geometric mean with SD. Open circles represent wild-type C57BL/6 mice; X’s represent animals deficient for TLR4 and MD2; red circles represent TLR4/MD2 -/- mice transgenic for human TLR4/MD2. Statistical comparisons are between C57BL/6 w.t. and hTLR4/MD2 KIKO groups. Statistical test was one-way ANOVA performed with family-wise error rate to adjust multiple comparisons; ns, p > 0.05; *, p < 0.05; **, p < 0.01; ***, p < 0.001.