Inhibition of Caspases Improves Bacterial Clearance in Experimental Peritonitis

BACKGROUND: Inhibition of caspases improves the antibacterial capacity of leukocytes cultured with peritoneal dialysis solutions, and improves the prognosis of septic, polymicrobial experimental peritonitis. OBJECTIVE: To test whether inhibition of caspases alters the evolution of peritonitis in the presence of peritoneal dialysis solution. DESIGN: 32 mice were assigned to therapy with either the pan-caspase inhibitor zVAD or vehicle for 48 hours following infection with Staphylococcus aureus, in the presence of lactate-buffered, 4.25% glucose peritoneal dialysis solution. 16 mice received vehicle in phosphate-buffered saline. MAIN OUTCOME MEASURE: Number of bacteria recovered from the peritoneum at 48 hours. RESULTS: Peritoneal dialysis solution accelerated leukocyte apoptosis. zVAD decreased the number of apoptotic peritoneal leukocytes and the number of bacteria recovered from the peritoneum at 48 hours (zVAD 2.8 +/- 0.3 vs vehicle 3.9 +/- 0.2 log colony forming units of S. aureus, p = 0.007). CONCLUSIONS: Inhibition of caspases accelerates peritoneal bacterial clearance in the presence of peritoneal dialysis solutions in vivo in the experimental setting. Inhibition of caspases should be explored as a mean to accelerate recovery following peritonitis in the clinical setting.