Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-3-2
pubmed:abstractText
Tumor necrosis factor alpha (TNFa) and lymphotoxin (LT) or TNF beta are closely linked cytokines produced by macrophages and activated T lymphocytes, which play important regulatory roles in the immune response to allografts. They have also been implicated as mediators of the adverse reactions observed during OKT3 therapy. Therefore, anti-TNF agents could be useful both for immunosuppression and for limiting the systemic response observed in patients receiving OKT3. Recombinant TNFR:Fc is a fusion protein that binds TNFa and LT, thereby neutralizing their effects in vitro. The present study investigates the potential clinical application of TNFR:Fc in a nonhuman primate renal allograft model. Cynomolgus renal allograft recipients were treated with TNFR:Fc induction therapy alone or in combination with subtherapeutic doses of cyclosporine. Control animals received no immunosuppression or subtherapeutic cyclosporine. TNFR:Fc, administered as the only immunosuppressive agent, successfully prolonged renal allograft survival in the majority of treated animals. The prolongation of allograft survival was even more impressive when TNFR:Fc was combined with subtherapeutic doses of cyclosporine. Onset of rejection was significantly delayed as well in the TNFR:Fc treated groups. No adverse side effects were observed in any of the TNFR:Fc treated animals. Precursor cytotoxic T cells were detected in peripheral blood samples of treated recipients but the level of effector CTLs in vivo was below the threshold of detection. These results demonstrate that TNFR:Fc can be safely administered and is effective in prolonging renal allograft survival and in delaying the onset of rejection when administered alone or in combination with cyclosporine.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0041-1337
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
300-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Inhibition of the effects of TNF in renal allograft recipients using recombinant human dimeric tumor necrosis factor receptors.
pubmed:affiliation
General Surgical Service, Massachusetts General Hospital, Boston.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't