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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1990-11-9
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pubmed:abstractText |
Untreated anephric LEW rats die ca. 9 days following transplantation of LBNF1 kidney allografts. Although treatment with ART-18, a mouse antirat IL-2R mAb (300 micrograms/kg/day x 10 days), prolonged graft survival to ca. 3 weeks, the severely impaired renal function was comparable to untreated controls (creatinine levels 3-5 mg/dl). In contrast, simultaneous infusion of ART-18 and a very low dose of CsA (0.75 mg/kg x 10 days), marginally effective on its own, resulted in survival of greater than 45 days; the grafts exhibited relatively good function comparable to that in rats treated with full-dose (15 mg/kg/day) CsA. This beneficial biological effect did not depend upon elevated CsA trough levels in animals conditioned with both modalities. The CD4:CD8 ratio at the graft site was lowest (0.3-0.4) in recipients treated with ART-18 + CsA. Synergy between the two agents has been demonstrated by adoptive transfer studies in which nonspecific suppression has been conferred selectively by cells infiltrating kidney grafts in rats given ART-18 and CsA in concert but not separately (LBNF1 and WF test cardiac allograft survival ca. 12 days). In contrast, suppression in the recipient spleens was donor-specific; both CD4 and CD8 cells prolonged test graft survival. Immunohistological evaluation of renal allografts revealed that therapy with ART-18 or low-dose CsA alone failed to deplete IL-2R+ cells and prevent production of IL-2, IFN-g, and TNF. In contrast, the frequency of infiltrating IL-2R+ cells and elaboration of endogenous cytokines in non-uremic hosts receiving combination therapy was greatly depressed, stressing again synergistic interaction between ART-18 and CsA. Additionally, markedly reduced class II antigen induction, XL-fibrin deposition, and glomerulitis may also contribute to prolonged survival and satisfactory function of kidney allografts in this animal group.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0041-1337
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
545-50
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2219270-Animals,
pubmed-meshheading:2219270-Antibodies, Monoclonal,
pubmed-meshheading:2219270-Creatinine,
pubmed-meshheading:2219270-Cyclosporins,
pubmed-meshheading:2219270-Graft Survival,
pubmed-meshheading:2219270-Immunotherapy, Adoptive,
pubmed-meshheading:2219270-Kidney,
pubmed-meshheading:2219270-Kidney Transplantation,
pubmed-meshheading:2219270-Male,
pubmed-meshheading:2219270-Rats,
pubmed-meshheading:2219270-Rats, Inbred Strains,
pubmed-meshheading:2219270-Receptors, Interleukin-2,
pubmed-meshheading:2219270-Spleen,
pubmed-meshheading:2219270-T-Lymphocytes,
pubmed-meshheading:2219270-Transplantation, Homologous,
pubmed-meshheading:2219270-Transplantation Immunology
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pubmed:year |
1990
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pubmed:articleTitle |
The mechanism of synergistic interaction between anti-interleukin 2 receptor monoclonal antibody and cyclosporine therapy in rat recipients of organ allografts.
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pubmed:affiliation |
Surgical Research Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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