COX inhibition alters phagocytosis, cytokine synthesis, and bacterial killing mechanisms in a cAMP-dependent manner. GBS was injected intraperitoneally to (A) WT mice dosed orally 1 hour earlier with indomethacin (dual COX inhibitor), SC-560 (COX1 inhibitor) or NS-398 (COX2 inhibitor) as well as to (B) COX1 knockout mice. Three hours after GBS injection (A-B) cAMP was measured in cell-free exudates while (C) phagocytosis and (D-E) NADPH oxidase activity was determined in total leukocytes. Cell-free exudate levels of (F-G) TNFα and IL-10 were also determined in NSAID-treated WTs and (H-I) COX1 knockouts. This COX-inhibited differential change in WT mice (J) bacterial killing, (K) NADPH oxidase activity and (L-M) cytokine synthesis was reversed by 15(S)-15 methyl PGE₂ (EP agonist) or db-cAMP given 5 minutes before GBS and therefore 55 minutes after NSAIDs. Data are represented and analyzed by an unpaired Student t test or ANOVA followed by either Dunnett or Bonferroni multiple comparison tests. Values are expressed as the mean ± SEM of 5-12 mice/group. * P <.05, ** P < .01, *** P < .001.