RGD Reference Report - Anti-tumor necrosis factor antibody enhances allograft survival in rats. - Rat Genome Database

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Anti-tumor necrosis factor antibody enhances allograft survival in rats.

Authors: Imagawa, DK  Millis, JM  Olthoff, KM  Seu, P  Dempsey, RA  Hart, J  Terasaki, PI  Busuttil, RW 
Citation: Imagawa DK, etal., J Surg Res. 1990 Apr;48(4):345-8.
RGD ID: 8548836
Pubmed: PMID:2338821   (View Abstract at PubMed)

We have recently observed significantly elevated serum tumor necrosis factor-alpha (TNF-alpha) levels during human liver allograft rejection. Although increased TNF activity has been reported in rejecting rat cardiac and renal allografts, this represents the first report of an animal model utilizing immunotherapy directed against TNF. Intraabdominal heart transplants (Buffalo to Lewis) were performed. Cardiac rejection was defined as cessation of a palpable beat and confirmed at laparotomy. Control animals received no immunotherapy and experienced rejection on Postoperative Day 11 +/- 0.4 (mean +/- SEM). Experimental animals received immunotherapy either intraperitoneally (ip) or intravenously (iv) from Days 1 to 10. Intraperitoneally administered anti-TNF-alpha prolonged graft survival to 16 +/- 2.7 days (P less than 0.05 vs controls), iv administration prolonged survival to 15 +/- 1.4 days (P less than 0.004). Animals treated with ip anti-TNF-beta survived 17 +/- 1.7 days (P less than 0.002 vs controls). Conversely, administration of purified TNF-alpha to graft recipients decreased graft survival to 7 +/- 0.4 days (P less than 0.001 vs controls). Serum samples analyzed in an L929 bioassay showed increased cytotoxic activity in control animals, corresponding to an increase in circulating TNF. This activity was partially abrogated in animals receiving immunotherapy. These data demonstrate that circulating levels of TNF are increased during rejection. Immunotherapy with anti-TNF-alpha or anti-TNF-beta prolongs graft survival, suggesting that TNF may play a role in the pathogenesis of acute allograft rejection.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LTAHumanTransplant Rejection treatmentISOLta (Rattus norvegicus) RGD 
LtaRatTransplant Rejection treatmentIMP  RGD 
LtaMouseTransplant Rejection treatmentISOLta (Rattus norvegicus) RGD 
TNFHumanTransplant Rejection treatmentISOTnf (Rattus norvegicus) RGD 
TnfRatTransplant Rejection treatmentIMP  RGD 
TnfMouseTransplant Rejection treatmentISOTnf (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lta  (lymphotoxin alpha)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Lta  (lymphotoxin A)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
LTA  (lymphotoxin alpha)
TNF  (tumor necrosis factor)


Additional Information