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.