We found that exposure of murine macrophages to ketamine inhibited TNF secretion by 18-34% after stimulation with CA-MRSA bacteria in the presence of antibiotics. The magnitude of the effect was comparable in response to both MW2 (USA400) and LAC (USA300) bacteria and was similar in the presence of either vancomycin (a lytic antibiotic associated with a greater TNF response to the bacteria) or daptomycin (a non-lytic antibiotic associated with a blunted TNF response to the bacteria). Our data suggest that ketamine administration to macrophages stimulated by CA-MRSA is associated with blunting of the TNF response to these virulent pathogens, and suggest that these findings may have therapeutic significance in MRSA sepsis. Furthermore, these data confirm and extend our previous observations that CA-MRSA bacteria exposed to daptomycin (versus vancomycin) trigger less TNF secretion by macrophages. The potentially beneficial antiinflammatory effects of daptomycin and ketamine were additive (Figures 2, 3) . Bacteria were added at a final concentration of 10 5 to10 7 CFU/mL (retrospective confirmation) in the presence of vancomycin at 20 μg/mL. One hour prior to stimulation, APV ("low" concentration of 300 μM or "high" concentration of 3 mM), ketamine (100 μM), or NMDA (30 μM) were added, alone or in combination, as indicated. Cells were then incubated for 18 hours; supernatants were collected and analyzed for TNF content by ELISA. The control lane represents the mean TNF macrophage production by macrophages not stimulated with bacteria. The mean includes wells exposed to APV, ketamine, or NMDA alone or in combination. In the absence of bacteria, TNF secretion was minimal and was not affected by APV, ketamine, or NMDA. Lanes 0-9 depict mean TNF secretion by macrophages exposed to vancomycin-treated MW2 alone (lane 0) or in the presence of the indicated concentrations of APV, ketamine, and/or NMDA (lanes 1-9). TNF secretion was reduced by approximately 30-40% when macrophages were pre-incubated with APV, ketamine, or APV + ketamine (lanes [1] [2] [3] [4] [5] . The magnitude of inhibition by ketamine and high-dose APV was similar and there were no additive or synergistic effect observed with combinations of ketamine and APV. Addition of NMDA (30 μΜ) led to a substantial increase in the amount of TNF secreted in response to the MW2 strain (lane 9), and this augmented response was blocked by both APV and ketamine. The "*" on "0.Control" and "8.NMDA+lo_APV" bars indicates significance at p < 0.05. The "**" on "0.Control_MW2" and "9.NMDA" bars indicates differences between the pretreated wells, and that TNF production after MRSA stimulation with NMDA substrate (9.NMDA) is significantly higher than that at the baseline MRSA stimulation (0.Control_MW2) at p < 0.05.