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.


METHODS
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.


METHODS
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.
Catalan
Marina Penélope
MP
Departments of Dialysis, Fundación Jiménez Díaz and Universidad Autónoma, Madrid, Spain.
Esteban
Jaime
J
Subirá
Dolores
D
Egido
Jesús
J
Ortiz
Alberto
A
D000590:Amino Acid Chloromethyl Ketones / Q000627:therapeutic use*; D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D015314:Dialysis Solutions / Q000494:pharmacology*; D004195:Disease Models, Animal; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010538:Peritonitis / Q000188:drug therapy* / Q000209:etiology* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000150:complications* / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification / Q000472:pathogenicity*
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015314:Dialysis Solutions; C426824:benzyloxycarbonyl-valyl-alanyl-(methyl)aspartic acid fluoromethyl ketone; D020169:Caspases