C3aR plays a role in enhanced inflammation in primary human macrophages and is expressed with caspase-5 in PMBCs from patients with sepsis. Primary MDMs were (A) untreated or treated with LPS for 1–3 h, or (B) untreated or treated with C3aRi, with and without LPS stimulation, for 3 h, and protein levels of pro-caspase-4, pro-caspase-5, caspase-5 p20, and β-actin were evaluated via Western blot. (C) MDMs were untreated or treated with C3aRi, with and without LPS, IFN-β, or IFN-γ for 3 h, and levels of phosphorylated p-38 or β-actin was evaluated via Western blot. (D) IL-6 and TNF cytokine release from MDMs was assessed via ELISA, 3 h after stimulation with LPS with or without C3aRi. Forest plots for random effects model estimates of effect size of the induction of (E) caspase-5 and C3aR1 genes in healthy controls versus patients with acute infections or sepsis in eight cohorts. Statistics analyzed via the unpaired Student’s t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001. Data are representative of at least three experiments (A–D), with three technical replicates each time.