C3aR contributes to amplification of proinflammatory mediators in the blood and to the severity of endotoxemia in mice. WT or C3aR-deficient (C3aR^−/−) BALBc mice were treated with a sublethal dose of LPS i.p. 2 h pt blood samples were collected and analyzed for expression of (A) caspase-11 or (B) IL-6. Fold-change of gene expression was calculated (Ctrl/LPS treated mice). 6 h pt, mice were treated with a lethal dose of LPS. Weight (C) and temperature (D) were monitored every 2 h for 20 h. Six control mice and eight treated mice were used. Next, WT mice were treated with the same regimen as described with or without C3aRi. As described above, 2 h pt (E) caspase-11 or (F) IL-6 expression was analyzed and fold-change of gene expression was calculated (Ctrl/LPS treated mice), and after 6 h mice were treated with a lethal dose of LPS. Weight (G) and temperature (H) were monitored every 2 h for 20 h. (I) WT mice were treated with LPS and with or without C3aRi i.p. 2 h pt, blood was collected via cardiac bleed and analyzed for IL-6 levels via ELISA. (J) WT mice were treated with LPS and with or without C3aRi, and survival was monitored. n = 5 mice/group in each independent experiment (E–J). Statistics analyzed via the unpaired Student’s t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001, ****, P < 0.0001. Data are representative of at least two (I–J) or three experiments (A–H), with three technical replicates each time.