Back to Program | 2010 Program and Abstracts Overview | 2010 Posters

Background and Aims: Despite the use of specific antibiotics, aggressive operative intervention, and nutritional support, peritoneal sepsis continues to be a major cause of morbidity and mortality. Local irrigation of the peritoneal cavity with a variety of agents has proven to be of no benefit. The brush border enzyme intestinal alkaline phosphatase (IAP) can detoxify gram-negative bacterial endotoxin lipopolysaccharides and systemic administration has been shown to be of benefit in several animal models of sepsis. The present study was designed to investigate the therapeutic effects of locally administered calf Intestinal alkaline phosphatase (cIAP) in a cecal ligation and puncture (CLP)-animal model of polymicrobial sepsis. Methods: Nine week old C57BL/6 male mice were randomized to undergo CLP with an 18 gauge needle, followed by instillation of cIAP into the peritoneal cavity at a variety of dosages and time schedules. Remote organ damage was evaluated by measurement of lung myeloperoxidase activity and blood levels of AST and ALT (liver enzymes). In addition, blood leukocyte counts and cytokine levels were assessed. Finally, peritoneal lavage fluid (PLF) was aspirated 24 h after CLP and neutrophil infiltration as well as bacterial counts in both aerobic and anaerobic conditions were determined. Results: We found that phosphatase activity due to cIAP in PLF was still present up to 5 h post injection. Compared to the vehicle-treated controls, the overall 7-day survival rate was increased by cIAP irrigation, with maximal effects seen at 25 units (40% vs. 0% survival rate). Compared to single cIAP injection (25 U), multiple injections of cIAP (25 U) or its co-administration with imipenem did not demonstrate significant additive effects on survival rate. cIAP-treated mice showed less lung neutrophil infiltration and liver damage compared to non-treated mice. cIAP treatment had no effects on the neutrophil counts, bacterial counts, or TNF-α levels in PLF, but there were reduced IL-6 levels in cIAP-treated animals compared to untreated mice (6,676 ± 1,322 pg/ml vs. 10,589 ± 248 pg/ml, respectively, p<0.05). Conclusions: These data demonstrate that local irrigation of the peritoneal cavity with cIAP enhances survival in a mouse model of peritonitis, likely through the reduction of local inflammation as well as remote organ damage. These results suggest that cIAP irrigation could be a novel therapy to treat intra-peritoneal sepsis.