Transplantation. 62(9):1371-1374, NOVEMBER 15TH, 1996
PMID: 8932291
Issn Print: 0041-1337
Publication Date: November 15th, 1996
IMMUNOMODULATORY PROPERTIES OF THE METAL CHELATORS DESFERRIOXAMINE AND DIETHYLENETRIAMINE PENTA-ACETIC ACID IN VITRO1
Martin Scholz;Roman Blaheta;Dirk Henrich;Jaroslav Cinatl;Bernd Markus;Hans Doerr;Jindrich Cinatl;
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Departments of Medical Virology and General Surgery and Gustav-Embden Zentrum der Biologischen Chemie, Johann Wolfgang Goethe University, 60596 Frankfurt am Main, Germany
Abstract
In this study, we investigated the effects of the intracellular metal chelator desferrioxamine (DFO) and the extracellular metal chelator diethylenetriamine penta-acetic acid (DTPA), which were previously shown to have strong anticytomegalovirus potencies, on their ability to elicit immunomodulatory effects in vitro[fcn,3]. The results showed that nontoxic and in vivo attainable concentrations of both DFO and DTPA inhibited mitogen- and allogen-induced proliferation of peripheral blood lymphocytes. The immunomodulatory effects of DFO/DTPA seem to be due to the impaired expression of interleukin-2 receptor and the reduced secretion of interleukin-2. However, metal chelators were more effective than cyclosporine or tacrolimus (FK506) in our in vitro experiments. Moreover, cytotoxicity mediated by lymphokine-activated killer cells and natural killer cells and the expression of HLA and adhesion molecules on cytokine-stimulated endothelial cells were differentially impaired by DFO/DTPA. These results warrant further study of the immunological effects of metal chelators in vivo.