Macrophage EPO signaling regulates resolution of E. coli-initiated infections. For (A–E), EPO-C, and EPOR-cKO mice were inoculated with 1 × 105 c.f.u. E. coli (n = 5 for each group at each time point), (A) Time course of peritoneal PMN numbers and resolution indices (n = 5). (B): Bacterial titers of peritoneal lavage fluids at 24 hrs (n = 5). (C) Changes in body temperatures expressed as mean of Δ°C (temperature at 24 h–temperature at 0 h, n = 5). (D) Percentage of apoptotic peritoneal leukocytes at 24 h (n = 5). (E) Inflammatory cytokines in peritoneal lavage fluids at 24 h (n = 3). For (F–J), WT mice were inoculated with 1 × 105 c.f.u. E. coli (n = 5 for each group at each time point) together with rhEPO (5,000 IU/kg) or PBS. (F) Time course of peritoneal PMN numbers and resolution indices (n = 5). (G) Bacterial titers of peritoneal lavage fluids at 24 hrs (n = 5). (H) Percentage of apoptotic peritoneal leukocytes at 24 hrs (n = 5). (I) Changes in body temperatures of (n = 5). (J) Inflammatory cytokines in peritoneal lavage fluids at 24 hrs (n = 3). (K) Percent survival of E. coli (5 × 107 c.f.u.) inoculated WT mice alone or with 5,000 IU/kg of rhEPO (n = 14 for each group). (L) Percent survival of E. coli (5 × 107 c.f.u.) inoculated EPO-C and EPOR-cKO mice (n = 14 for each group). For M-N, WT mice were inoculated with 1 × 105 c.f.u. E. coli, 12 hours after infection, mice were treated with rhEPO (5,000 IU/kg) or PBS (n = 5 for each group), and 12 hours after rhEPO treatment, mice were sacrificed for measurement. (M) Peritoneal PMN numbers (n = 5). (N) Bacterial titers of peritoneal lavage fluids (n = 5). Data are representative of at least two independent experiments. Results were expressed as mean ± SEM. *P < 0.05, **P < 0.01, and ****P < 0.0001. Statistics: unpaired two-tailed Student’s t-test (B, D, H, M, N), one-way ANOVA with Tukey’s post hoc test for multiple comparisons (C, E, G, I, J) or Log-Rank test (K, L).