Figure 4. SPM and antibiotics accelerate resolution and enhance bacterial killing.

(a-c) Mice were inoculated with E. coli (10⁵ CFU), RvD1 methyl ester (50 ng), and ciprofloxacin (Cipro, 50 ng). (a) Exudate PMN numbers and resolution indices. (b) Bacterial titers. (c) 14-HDHA and PD1 levels determined using LC-MS-MS-based LM-lipidomics. Results are expressed as mean±s.e.m. *p<0.05, **p<0.01, vs. E. coli alone; ^#p<0.05, ^##p<0.01, vs. E. coli+RvD1; ^§p<0.05, vs. E. coli+Cipro. Gray, E. coli alone; blue, E.coli+RvD1; green, E.coli+Cipro; dark blue, E.coli+RvD1+Cipro. (d) Mice were inoculated with E. coli (10⁷ CFU), SPM panel (RvD1, RvD5 and PD1; 50 ng each) and Cipro (25 μg). Body temperatures and bacterial titers were determined at 24h. Results are expressed as mean±s.e.m. *p<0.05, **p<0.01, ***p<0.001 vs. E. coli alone; ^#p<0.05, ^##p<0.01 vs. E. coli+SPM; ^§p<0.05, vs. E. coli+Cipro. (e,f) Murine dorsal pouches were given live S. aureus (10⁵ CFU) alone, plus SPM (RvD1, RvD5, PD1 at 100 ng each per mouse), vancomycin (Vanco, 2.5 μg), or both SPM and vancomycin by intra-pouch injection, pouch exudates were collected at 24h. (e) PMN and bacterial counts (CFU). Results are expressed as mean±s.e.m. *p<0.05, **p<0.01 vs. S. aureus alone; ^#p<0.05, vs. S. aureus+SPM; ^§§p<0.01, vs. S. aureus+Vanco. (f) Skin-pouch biopsies (Magnifications 40X). Arrows denote PMN infiltration into pouch linings. PC, pouch cavity. L, linings. Animal numbers are denoted within brackets (a) or bars (b-e).