Linked Life Data

20386495

Source:http://linkedlifedata.com/resource/pubmed/id/20386495

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-10-22
pubmed:abstractText
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 TNF?, 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1540-0514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
535-44
pubmed:meshHeading
pubmed-meshheading:20386495-Animals, pubmed-meshheading:20386495-Burns, pubmed-meshheading:20386495-Concanavalin A, pubmed-meshheading:20386495-Deoxycytidine, pubmed-meshheading:20386495-Drug Evaluation, Preclinical, pubmed-meshheading:20386495-Interleukin-10, pubmed-meshheading:20386495-Interleukin-6, pubmed-meshheading:20386495-Leukocyte Count, pubmed-meshheading:20386495-Lipopolysaccharides, pubmed-meshheading:20386495-Lymphocyte Activation, pubmed-meshheading:20386495-Macrophages, pubmed-meshheading:20386495-Male, pubmed-meshheading:20386495-Mice, pubmed-meshheading:20386495-Mice, Inbred C57BL, pubmed-meshheading:20386495-Monocytes, pubmed-meshheading:20386495-Myeloid Cells, pubmed-meshheading:20386495-Nitric Oxide, pubmed-meshheading:20386495-Peptidoglycan, pubmed-meshheading:20386495-Pseudomonas Infections, pubmed-meshheading:20386495-Ribonucleotide Reductases, pubmed-meshheading:20386495-Spleen, pubmed-meshheading:20386495-T-Lymphocyte Subsets, pubmed-meshheading:20386495-Tumor Necrosis Factor-alpha
pubmed:year
2010
pubmed:articleTitle
A ribonucleotide reductase inhibitor reverses burn-induced inflammatory defects.
pubmed:affiliation
Shriners Hospital for Children, Cincinnati, Ohio 45229, USA. gnoel@shrinenet.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't