EFFICACY OF TREATMENT WITH THE IRON(III) COMPLEX OF DIETHYLENETRIAMINE PENTAACETIC ACID IN MICE AND PRIMATES INOCULATED WITH LIVE LETHAL DOSE-100 ESCHERICHIA-COLI

The iron (III) complex of diethylenetriamine pentaacetic acid (DTPA ir on [III]) protected mice and baboons from the lethal effects of an inf usion with live LD(100) Escherichia coli, in mice, optimal results wer e obtained when DTPA iron (III) was administered two or more hours aft er infection. Prevention of death occurred in spite of the fact that t he adverse effects of TNF-alpha were well underway in the mouse model. The half-life of DTPA iron (III) was 51+/-9 min in normal baboons; pr imary clearance was consistent with glomerular filtration. In septic b aboons, survival was observed after administration of two doses of DTP A iron (III) at 2.125 mg/kg, the first one given before, or as late as 2 h after, severe hypotension. Administration of DTPA iron (III) did not alter mean systemic arterial pressure, but did protect baboons in the presence of high levels of TNF-alpha and free radical overproducti on. Furthermore, exaggerated production of nitric oxide was attenuated , The mechanism of protection with DTPA iron (III) is not obvious, Bec ause of its ability to interact in vitro with free radicals, its poor cell permeability, and its short half-life, we postulate that DTPA iro n (III) and/or its reduced form may have protected the mice and baboon s by sequestration and subsequent elimination of free radicals (includ ing nitric oxide) from their systems.