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 di ethylenetriamine penta-acetic acid (DTPA), which were previously shown to have strong anticytomegalovirus potencies, on their ability to eli cit immunomodulatory effects in vitro[fcn,3], The results showed that nontoxic and in vivo attainable concentrations of both DFO and DTPA in hibited 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 s ecretion of interleukin-2. However, metal chelators were more effectiv e 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 molecu les on cytokine-stimulated endothelial cells were differentially impai red by DFO/DTPA. These results warrant further study of the immunologi cal effects of metal chelators in vivo.