Linked Life Data

9247586

Source:http://linkedlifedata.com/resource/pubmed/id/9247586

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1997-8-25
pubmed:abstractText
Antibodies to tumor necrosis factor (TNF)-alpha have been recently proposed as effective treatment for patients with Crohn's disease. Here, we analyze the functional role of TNF-alpha in a mouse model of chronic intestinal inflammation induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that mimics some characteristics of Crohn's disease in humans. Macrophage-enriched lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis produced 10-30-fold higher levels of TNF-alpha mRNA and protein than cells from control mice. When mice with chronic colitis were treated by intraperitoneal injection of antibodies to TNF-alpha, an improvement of both the clinical and histopathologic signs of disease was found. Isolated macrophage-enriched LP cells from anti-TNF-alpha-treated mice produced strikingly less pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant role of TNF-alpha in the mouse TNBS-induced colitis model was further underlined by the finding that striking colonic inflammation and lethal pancolitis was induced in TNF-alpha-transgenic mice upon TNBS treatment. Conversely, no significant TNBS-induced colitis could be induced in mice in which the TNF-alpha gene had been inactivated by homologous recombination. Complementation of TNF-alpha function in TNF-/- mice by the expression of a mouse TNF-alpha transgene was sufficient to reverse this effect. Taken together, the data provide direct evidence for a predominant role of TNF-alpha in a mouse model of chronic intestinal inflammation and encourage further clinical trials with antibodies to TNF-alpha for the treatment of patients with Crohn's disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1743-50
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice.
pubmed:affiliation
Laboratory of Immunology, I. Medical Clinic, University of Mainz, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't