Linked Life Data

11687457

Source:http://linkedlifedata.com/resource/pubmed/id/11687457

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-11-5
pubmed:abstractText
Clinical studies have shown positive associations among sustained and intense inflammatory responses and the incidence of bacterial infections. Patients presenting with acute respiratory distress syndrome (ARDS) and high levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6, have increased risk for developing nosocomial infections attributable to organisms such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter spp., compared to those patients with lower levels. Our previous in vitro studies have demonstrated that these bacterial strains exhibit enhanced growth extracellularly when supplemented with high concentrations of pure recombinant TNF-alpha, IL-1 beta, or IL-6. In addition, we have shown that the intracellular milieu of phagocytic cells that are exposed to supraoptimal concentrations of TNF-alpha, IL-1 beta, and IL-6 or lipopolysaccharide (LPS) favors survival and replication of ingested bacteria. Therefore, we hypothesized that under conditions of intense inflammation the host's micromilieu favors bacterial infections by exposing phagocytic cells to protracted high levels of inflammatory cytokines. Our clinical studies have shown that methylprednisolone is capable of reducing the levels of TNF-alpha, IL-1 beta, and IL-6 in ARDS patients. Hence, we designed a series of in vitro experiments to test whether human monocytic cells (U937 cells) that are activated with high concentrations of LPS, which upregulate the release of proinflammatory cytokines from these phagocytic cells, would effectively kill or restrict bacterial survival and replication after exposure to methylprednisolone. Fresh isolates of S. aureus, P. aeruginosa, and Acinetobacter were used in our studies. Our results indicate that, compared with the control, stimulation of U937 cells with 100-ng/ml, 1.0-microg/ml, 5.0-microg/ml, or 10.0-microg/ml concentrations of LPS enhanced the intracellular survival and replication of all three species of bacteria significantly (for all, P = 0.0001). Stimulation with < or =10.0 ng of LPS generally resulted in efficient killing of the ingested bacteria. Interestingly, when exposed to graded concentrations of methylprednisolone, U937 cells that had been stimulated with 10.0 microg of LPS were able to suppress bacterial replication efficiently in a concentration-dependent manner. Significant reduction in numbers of CFU was observed at > or =150 microg of methylprednisolone per ml (P values were 0.032, 0.008, and 0.009 for S. aureus, P. aeruginosa, and Acinetobacter, respectively). We have also shown that steady-state mRNA levels of TNF-alpha, IL-1 beta, and IL-6 in LPS-activated cells were reduced by treatment of such cells with methylprednisolone, in a concentration-dependent manner. The effective dose of methylprednisolone was 175 mg, a value that appeared to be independent of priming level of LPS and type of mRNA. We therefore postulate that a U-shaped relationship exists between the level of expression of TNF-alpha, IL-1 beta, and IL-6 within the phagocytic cells and their abilities to suppress active survival and replication of phagocytized bacteria.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-10338488, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-10471625, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-11076706, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-1728986, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-1833820, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-1900241, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-1901893, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-2019445, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-7587434, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-7587435, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-7664886, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-7705118, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-7865982, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-8381771, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-8486849, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-8557986, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-8594414, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-8805654, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-8814466, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-8980983, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-9149588, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-9218498, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-9559600, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-9590259, http://linkedlifedata.com/resource/pubmed/commentcorrection/11687457-9669790
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1071-412X
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1156-63
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Effects of methylprednisolone on intracellular bacterial growth.
pubmed:affiliation
Pulmonary and Critical Care Medicine/Memphis Lung Research Program, Department of Medicine, University of Tennessee, Memphis, Tennessee 38163, USA. umeduri@utmem.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't