Linked Life Data

8436831

Source:http://linkedlifedata.com/resource/pubmed/id/8436831

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1993-3-24
pubmed:abstractText
TNF, a cytokine with multiple properties, is known to be rapidly inactivated in vivo. In patients with septic shock and kidney malfunction, conflicting data have been reported regarding the presence of TNF in the circulation. Recently, we have shown that these differences can be the result of the detection of free TNF vs TNF complexed with soluble TNF-R. Enhanced levels of soluble TNF-R have been reported in patients with kidney malfunction. Because the kidney is thought to play an important role in TNF and TNF-R metabolism, we investigated the influence of bilateral nephrectomy on TNF clearance and TNF-R regulation in a murine model. The data obtained show that bilateral nephrectomy results in circulating levels of immunologically detectable (ELISA), but not biologically active (bioassay), TNF. Injection of endotoxin results in significantly higher levels of immunologically detectable TNF in bilaterally nephrectomized mice, compared with sham-operated mice, whereas biologically active levels were similar. To investigate the roles of TNF-R1 (P55) and TNF-R2 (P75) in this process, clearance of TNF was studied by injection of murine and human TNF. Murine TNF injection leads to comparable clearance of bioactive TNF in nephrectomized and sham-operated mice (t1/2 = approximately 12 min). However, clearance of immunologically detectable murine TNF is significantly slower in nephrectomized mice, compared with sham-operated mice (t1/2 = 96 min vs 26 min, respectively; p < 0.05). Administration of human TNF results in a significantly lower clearance in nephrectomized mice, compared with sham-operated mice (t1/2 = 108 min vs 25 min, respectively; p < 0.05). This is observed for both bioactive human TNF and immunologically detectable human TNF. Based on the fact that murine TNF-R1 (55 kDa) has a similar affinity for murine and human TNF, whereas murine TNF-R2 (75 kDa) shows affinity only for murine TNF, the data obtained suggest an important role for TNF-R2 in inactivation and clearance of TNF by the kidney. Moreover, the data suggest that kidney malfunction affects TNF clearance, leading to increased amounts of circulating TNF-TNF-R complexes, which could function as a slow release reservoir for TNF.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
150
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2007-17
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Influence of nephrectomy on tumor necrosis factor clearance in a murine model.
pubmed:affiliation
Department of Surgery, Faculty II, University of Limburg, Maastricht, The Netherlands.
pubmed:publicationType
Journal Article