Shiga toxins(Stxs), which are produced by enterohemorrhagic Escherichia coli and Shigella dysenteriae serotype I, induce proinflammatory cytokines including tumor necrosis factor-alpha, interleukin(IL)-1 beta, IL-6, interferon-gamma, and chemokines such as IL-8 in intestinal epithelial cells, vascular endothelial cells, and monocytes/macrophages in vitro and in kidneys and spleen in vivo. Cytokines induced by Stxs and lipopolysaccharide enhance the toxicity of Stxs via up-regulation of the expression of Gb3, a Stx receptor, and infiltration of neutrophils. Stxs bind to neutrophils and transmigrate across intestinal mucosa and are transported to the target organs through bloodstreams. Stxs induce cytokines in vascular endothelial cells and peripheral blood monocytes and may injure organ tissues, finally resulting in hemolytic uremic syndrome and encephalopathia.
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