An animal model of haemolytic--uraemic syndrome in shigellosis: lipopolysaccharides of Shigella dysenteriae I and S. flexneri produce leucocyte-mediated renal cortical necrosis in rabbits

Abstract

To develop an animal model of the haemolytic-uraemic syndrome during shigellosis, rabbits were injected with lipopolysaccharides (LPS) extracted by the hot phenol-water method from Shigella dysenteriae I and from S. flexneri. Two intravenous injections of LPS spaced by 24 h elicited renal cortical necrosis in a generalized Shwartzman reaction characterized by fibrin deposition in glomerular capillaries and by elevated plasma creatinine concentration. Rabbits rendered leucopenic by busulphan treatment were protected against renal cortical necrosis after injection with LPS derived from S. dysenteriae I. Both LPS preparations derived from Shigella species were also active in producing fever in rabbits, death in rabbits, and gelation of limulus lysate with approximately the same potency as a standard LPS of E. coli 055:B5. These results demonstrated that the LPS of Shigella species given intravenously to rabbits produces renal cortical necrosis, which is caused by leucocyte-mediated intravascular fibrin deposition in renal blood vessels and which resembles histologically the renal lesion in the haemolytic-uraemic during shigellosis in humans