Cyclosporine and anti-interleukin 2 receptor monoclonal antibody therapy suppress accelerated rejection of rat cardiac allografts through different effector mechanisms

Transplantation
W W HancockJ W Kupiec-Weglinski

Abstract

Increasing numbers of sensitized patients are either precluded from receiving an allograft or experience accelerated rejection which may be refractory to conventional therapy. Using a rat model, we have shown that accelerated (24 hr) rejection of LBN cardiac Tx in LEW rats sensitized with BN skin grafts 7 days earlier, could be prevented by treatment with cyclosporine (15 mg/kg/day x7 days, Tx survival about 42 days) or ART-18, an anti-IL-2R mAb (300 micrograms/kg/day x10 days i.v., Tx survival about 16 days). In this study, we evaluated intragraft mechanisms responsible for these effects by immunoperoxidase localization of relevant humoral mediators (IgG, IgM, C3, cross-linked fibrin), graft infiltrating cells (GIC), and associated cytokines (IL-2, IFN-g, tumor necrosis factor [TNF], or cytokine receptors (IL-2R). Tx rejected in fulminating fashion by 24 hr in sensitized hosts showed extensive and progressive endothelial deposition of IgG, C3, and fibrin from 2 hr, followed by an influx of neutrophils at 3 hr, and peak numbers of GIC by 18 hr (88.8 +/- 20.3 leukocytes/field). At 18 hr, GIC consisted of neutrophils (26%), T cells (20%, greater than 90% of which were OX-8+), and monocytes/macrophages (53%), whereas B cells were ...Continue Reading

Citations

Jan 1, 1994·Life Sciences·J A Wald, W J Jusko
Nov 1, 1993·Journal of the American College of Cardiology·S H JennisonL W Miller
Aug 15, 2002·Transplantation Proceedings·G S SchmidbauerK Schwemmle
Nov 15, 2002·Transplantation Proceedings·G SchmidbauerK Schwemmle
Jan 1, 1994·Annals of Surgery·U W HeemannN L Tilney
Dec 1, 1993·Immunological Reviews·L MakowkaD V Cramer
May 1, 1997·The American Journal of the Medical Sciences·T H Stadlbauer, J W Kupiec-Weglinski
Jul 1, 1994·Cell Adhesion and Communication·A J CoitoJ W Kupiec-Weglinski
Nov 30, 1993·Annals of the New York Academy of Sciences·D V CramerL Makowka
Oct 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuan ZhaiJerzy W Kupiec-Weglinski

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