Linked Life Data

15983903

Source:http://linkedlifedata.com/resource/pubmed/id/15983903

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2005-6-28
pubmed:abstractText
Klebsiella pneumoniae is a leading cause of pneumonia due to gram-negative bacteria. A significant clinical complication of pulmonary infection with K. pneumoniae is peripheral blood dissemination, which results in a systemic infection coincident with the localized pulmonary infection. This study describes the critical importance of tumor necrosis factor (TNF) receptor 1 (TNFR1)-mediated signaling during K. pneumoniae bacteremia. TNFR1-deficient mice displayed a significantly increased mortality rate after intravenous inoculation. Unexpectedly, this increased mortality occurred in the absence of either increased bacterial burden or increased liver injury. However, excessive production of proinflammatory cytokines, including TNF-alpha , was observed in TNFR1-deficient mice, compared with that observed in infected C57BL/6 mice, which suggests that production was dysregulated in the absence of TNFR1 signaling. In contrast, other experiments examined the effect of immunotherapy with anti-TNF-alpha during K. pneumoniae bacteremia. Administration of a neutralizing anti-TNF-alpha antibody completely ablated K. pneumoniae-induced liver injury. This reduction in liver injury failed to translate into an improved survival rate, because mice died of the infection as late as 10 days after infection. Bacterial clearance after neutralization of TNF-alpha was significantly impaired at later time points during infection. Diminished production of liver-associated cytokines and chemokines correlated with impaired bacterial clearance, which suggests that antibacterial immune responses were dampened. These data indicate that the antibacterial host response is dysregulated in mice lacking TNFR1 or TNF-alpha bioactivity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1537-6591
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
41 Suppl 3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S213-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Defective innate antibacterial host responses during murine Klebsiella pneumoniae bacteremia: tumor necrosis factor (TNF) receptor 1 deficiency versus therapy with anti-TNF-alpha.
pubmed:affiliation
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0642, USA. tmoore@umich.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural