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01-05-2011 | Original Article

Local Peritoneal Irrigation with Intestinal Alkaline Phosphatase Is Protective Against Peritonitis in Mice

Authors: Farzad Ebrahimi, Madhu S. Malo, Sayeda Nasrin Alam, Angela K. Moss, Halim Yammine, Sundaram Ramasamy, Brishti Biswas, Kathryn T. Chen, Nur Muhammad, Golam Mostafa, H. Shaw Warren, Elizabeth L. Hohmann, Richard A. Hodin

Published in: Journal of Gastrointestinal Surgery | Issue 5/2011

Abstract

Background

The brush-border enzyme intestinal alkaline phosphatase (IAP) functions as a gut mucosal defense factor and detoxifies different toll-like receptor ligands. This study aimed to determine the therapeutic effects of locally administered calf IAP (cIAP) in a cecal ligation and puncture (CLP) model of polymicrobial sepsis.

Methods

C57BL/6 mice underwent CLP followed by intraperitoneal injection of cIAP or normal saline. Blood leukocyte counts, levels of cytokines and liver enzymes, and lung myeloperoxidase activity were determined. Peritoneal lavage fluid (PLF) was assayed for neutrophil infiltration and both aerobic and anaerobic bacterial counts.

Results

After intraperitoneal injection, cIAP activity in PLF decreased 50% within 15 min with minimal activity evident at 4 h. Compared with irrigation with normal saline, cIAP irrigation increased the 7-day survival rate in mice undergoing CLP, with maximal effects seen at 25 units of cIAP (0% vs. 46% survival rate, respectively; p < 0.001). cIAP treatment reduced lung inflammation, liver damage and levels of tumor necrosis factor alpha and interleukin-6.

Conclusions

Peritoneal irrigation with cIAP significantly enhances survival in a mouse model of peritonitis, likely through reduction of local inflammation and remote organ damage. We suggest that intraperitoneal cIAP irrigation could be a novel therapy for intra-abdominal sepsis.

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Title: Local Peritoneal Irrigation with Intestinal Alkaline Phosphatase Is Protective Against Peritonitis in Mice
Authors: Farzad Ebrahimi
Madhu S. Malo
Sayeda Nasrin Alam
Angela K. Moss
Halim Yammine
Sundaram Ramasamy
Brishti Biswas
Kathryn T. Chen
Nur Muhammad
Golam Mostafa
H. Shaw Warren
Elizabeth L. Hohmann
Richard A. Hodin
Publication date: 01-05-2011
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 5/2011
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-010-1405-6

At a glance: The STEP trials

Springer Medicine

Local Peritoneal Irrigation with Intestinal Alkaline Phosphatase Is Protective Against Peritonitis in Mice

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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