Immunomodulatory properties of the metal chelators desferrioxamine and diethylenetriamine penta-acetic acid in vitro.
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.
Scholz
M
M
Department of Medical Virology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Blaheta
R A
RA
Henrich
D
D
Cinatl
J
J
Markus
B H
BH
Doerr
H W
HW
Cinatl
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D004369:Pentetic Acid / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D002614:Chelating Agents; D004369:Pentetic Acid; D003676:Deferoxamine