| A ribonucleotide reductase inhibitor reverses burn-induced inflammatory defects. | |
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MedLine Citation:
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PMID: 20386495 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Immature myeloid cells have been implicated as a source of postburn inflammation, and the appearance of these cells correlates with enhanced upregulation of hematopoiesis. The role of proliferative cells in postburn immune changes has not been directly tested. Gemcitabine, a ribonucleotide reductase inhibitor, has been shown to deplete proliferative immature myeloid cells in tumor models while sparing mature cells, leading to restored lymphocyte function and tumor regression. We treated burn mice at postburn day 6 (PBD6) with 120 mg/kg gemcitabine. On PBD8, splenocytes were taken and stimulated with LPS, peptidoglycan, or concanavalin A. The blood and spleen cell populations were enumerated by flow cytometry or automated cell counter. In addition, mice treated with gemcitabine were given LPS or infected with Pseudomonas aeruginosa at PBD8, and mortality was monitored. Gemcitabine depleted burn-induced polymorphonuclear leukocytes and inflammatory monocytes without affecting mature F4/80 macrophages. This was accompanied by reduced TNFα, IL-6, and IL-10 production by burn splenocytes. Burn splenocytes stimulated with mitogens exhibited increased nitric oxide production relative to sham mice. In vivo treatment of burn mice with gemcitabine blocked these burn-induced changes without damaging lymphocyte function. Treatment of burn mice with gemcitabine ameliorated burn-induced susceptibility to LPS and infiltration of polymorphonuclear leukocytes into the liver and lung. Finally, gemcitabine treatment blocked the protective effect of burn injury upon P. aeruginosa infection. Our report shows that proliferative cells are major drivers of postburn immune changes and provides evidence that implicates immature myeloid cells in these processes. |
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Authors:
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Greg Noel; Quan Wang; Andrew Osterburg; Sandy Schwemberger; Laura James; Lauren Haar; Nicholas Giacalone; Ingrid Thomas; Cora Ogle |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 34 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 535-44 Citation Subset: IM |
Affiliation:
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Shriners Hospital for Children, Cincinnati, Ohio 45229, USA. gnoel@shrinenet.org |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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