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

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Journal of Gastrointestinal Surgery Aims and scope

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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Acknowledgments

This work was supported by NIH grants R01DK050623 and R01DK047186 to RAH, and a Junior Faculty Award from the MGH Department of Surgery and a Grand Challenge Exploration Grant from the Bill and Melinda Gates Foundation to MSM.

Competing interests

The authors declare no conflicting financial interests.

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Authors and Affiliations

  1. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Jackson 812, 55 Fruit Street, Boston, MA, 02114, USA

    Farzad Ebrahimi, Madhu S. Malo, Sayeda Nasrin Alam, Angela K. Moss, Halim Yammine, Sundaram Ramasamy, Brishti Biswas, Kathryn T. Chen, Nur Muhammad, Golam Mostafa & Richard A. Hodin

  2. Infectious Disease Unit, Departments of Pediatrics and Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA

    H. Shaw Warren

  3. Infectious Disease Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA

    Elizabeth L. Hohmann

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  1. Farzad Ebrahimi
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Correspondence to Madhu S. Malo.

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Ebrahimi, F., Malo, M.S., Alam, S.N. et al. Local Peritoneal Irrigation with Intestinal Alkaline Phosphatase Is Protective Against Peritonitis in Mice. J Gastrointest Surg 15, 860–869 (2011). https://doi.org/10.1007/s11605-010-1405-6

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  • DOI: https://doi.org/10.1007/s11605-010-1405-6

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