Response to shiga toxin-1, with and without lipopolysaccharide, in a primate model of hemolytic uremic syndrome

Shiga toxin (Stx) and lipopolysaccharide (LPS) both participate in the path ogenesis of post-diarrheal hemolytic uremic syndrome (HUS), yet little is k nown about the factors that modulate the host response to these toxins. We have previously shown that the baboon develops HUS if 100 ng/kg of purified Stx-1 is administered rapidly as a single bolus, but not if it is given as four 25-ng/kg doses every 12 h. We therefore used this baboon model to stu dy the response to small intravenous doses of Stx-1, with and without the c o-administration of LPS. The coadministration of two 1-mg/kg doses of LPS ( given at 0 and 24 h) and four 25-ng/kg doses of Stx-1 (given at 0, 12, 24, and 36 h) resulted in HUS, but the administration of either toxin separatel y did not. The development of HUS was associated with a rise in urinary, bu t not plasma concentrations of TNF, and a rise in both urinary and plasma c oncentrations of IL-6 and IL-8. We speculate that LPS is not required for d isease expression in the human, but that it can augment the response to oth erwise subtoxic amounts of Stx and this augmentation may be mediated by LPS -induced cytokine release. Copyright (C) 2001 S. Karger AG, Basel.