A laboratory model of toxin-induced hemolytic uremic syndrome

A laboratory model of toxin-induced hemolytic uremic syndrome.BackgroundVerocytotoxin-producing (Shiga-like toxin-producing) Escherichia coli infection is the principal cause of hemolytic uremic syndrome (HUS). The pathogenesis is unclear, and there is a need for animal models. These are impeded by the different distribution of verocytotoxin receptors between species. We have circumvented this restriction using ricin, which gains entry into cells via various galactose receptors. Like verocytotoxin, ricin specifically cleaves a single adenine from ribosomal RNA.MethodsRats were given ricin at a dose of 6.7 μg/100g body wt, with or without lipopolysaccharide at 10 μg/100g body wt. Lipopolysaccharide alone or saline were used as controls. Changes in glomerular filtration rate, hematological parameters, histology, and plasma cytokine concentrations were measured.ResultsExtensive glomerular thrombosis, pyknotic nuclei, and an infiltration of ED1-positive cells into glomeruli were observed eight hours after an injection of ricin. Other vascular beds were unaffected. Histologic changes were preceded by oliguric renal failure, hemolysis, and thrombocytopenia. Ricin produced a rise in plasma concentrations of monocyte chemotactic protein-1, > tumor necrosis factor-α, > interleukin-1β, > interleukin-6. Interferon-γ showed a small increase at the end of the experiment.ConclusionsRicin induces glomerular thrombotic microangiopathy, closely resembling that which occurs in verocytotoxin-producing E. coli–induced HUS. As in HUS, high concentrations of proinflammatory cytokines are present, which are probably a result of cytokine superinduction by the toxin