Document Detail

Neutrophil elastase inhibitor restores gut ischemia reperfusion-induced impairment of gut immunity with reduced plasma interleukin-6 concentrations in mice.
MedLine Citation:
PMID:  20969469     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: Gut-associated lymphoid tissue (GALT) is regarded as central mucosa-associated lymphoid tissue that influences systemic mucosal immunity. Our previous study revealed that gut ischemia and reperfusion (I/R) reduces GALT lymphocyte numbers. Because gut hypoperfusion frequently occurs in trauma, shock, and surgery patients, establishment of a therapeutic method to preserve GALT mass after gut I/R may be important for the prevention of infections. We examined the effects of sivelestat sodium hydrate, a selective inhibitor of neutrophil elastase, on GALT mass and plasma cytokine concentrations in a murine gut I/R model.
METHODS: Seventy male ICR mice were randomized to the control (n = 34) or the sivelestat (n = 36) group. After intravenous cannulation of the animals, the superior mesenteric artery was occluded for 60 min. After reperfusion, physiologic saline or sivelestat 5 mg/kg hourly was infused for 24 h. Sixteen mice in the control and 22 in the sivelestat group were alive at 24 h. Twenty-six mice (n = 13 in each group) were chosen randomly for harvest of the small intestine. Lymphocytes from Peyer patches (PP), the intraepithelial space (IE), and the lamina propria (LP) were counted; and their phenotypes (αβT-cell receptor (TCR), γδTCR, CD4, CD8, B cell) were determined by flow cytometry. Cytokine concentrations (interleukin [IL]-6, IL-1β, IL-10) in the plasma and bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay.
RESULTS: Sivelestat treatment did not improve survival but increased PP and IE lymphocyte numbers significantly and reduced the LP CD8(+) cell percentage and plasma IL-6 concentration compared with controls. There were no significant differences between the two groups in other cell phenotypes or cytokine concentrations.
CONCLUSION: Sivelestat treatment after gut I/R may be useful for maintaining gut immunity and preventing systemic inflammatory responses.
Kazuhiko Fukatsu; Kazuya Tanabe; Yoshinori Maeshima; Jiro Omata; Hiroshi Yasuhara; Daizoh Saitoh
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Surgical infections     Volume:  11     ISSN:  1557-8674     ISO Abbreviation:  Surg Infect (Larchmt)     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-25     Completed Date:  2011-01-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815642     Medline TA:  Surg Infect (Larchmt)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  517-22     Citation Subset:  IM    
Surgical Center, The University of Tokyo, Tokyo, Japan.
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MeSH Terms
Disease Models, Animal
Enzyme Inhibitors / therapeutic use*
Flow Cytometry
Gastrointestinal Tract / immunology*
Glycine / analogs & derivatives*,  therapeutic use
Interleukin-6 / blood*
Intestinal Mucosa / immunology,  pathology
Ischemia / immunology*
Leukocyte Elastase / antagonists & inhibitors*
Lymphocyte Count
Lymphocyte Subsets / immunology
Mice, Inbred ICR
Sulfonamides / therapeutic use*
Survival Analysis
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Interleukin-6; 0/Sulfonamides; 127373-66-4/ONO 5046; 56-40-6/Glycine; EC Elastase

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