Response to Shiga toxin 1 and 2 in a baboon model of hemolytic uremic syndrome.
Post-diarrheal (D+) hemolytic uremic syndrome (HUS) is caused by Shiga-toxin (Stx)-producing Escherichia coli. There is epidemiological, cell culture, and mouse model evidence that Stx2-producing E. coli are more likely to cause HUS than strains that produce only Stx1, but this hypothesis has not been tested in a primate model of HUS. We have developed a baboon model of Stx-mediated HUS that was employed to compare the clinical, cytokine, and histological response to equal amounts of the two Shiga toxins. Animals given IV Stx2 developed progressive thrombocytopenia, hemolytic anemia, and azotemia, and urinary interleukin-6 levels rose significantly. Glomerular thrombotic microangiopathy was found at necropsy. Animals given Stx1 showed no cytokine response and no clinical, laboratory, or histological signs of HUS. Our findings from the primate model corroborate previous epidemiological, cell culture, and mouse model observations, and suggest that enteric infection with Stx2-producing E. coli is more likely to cause HUS than infection with organisms that produce only Stx1.
Siegler
Richard L
RL
Division of Pediatric Nephrology and Hypertension, Department of Pediatrics, 50 North 1900 East, 2B422, Salt Lake City, UT 84132-2204, USA. dick.siegler@hsc.utah.edu
Obrig
Tom G
TG
Pysher
Theodore J
TJ
Tesh
Vernon L
VL
Denkers
Nathaniel D
ND
Taylor
Fletcher B
FB
D000743:Anemia, Hemolytic / Q000209:etiology; D000818:Animals; D004195:Disease Models, Animal; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology* / Q000473:pathology / Q000652:urine; D015850:Interleukin-6 / Q000652:urine; D010215:Papio; D022622:Shiga Toxin 1 / Q000633:toxicity*; D022641:Shiga Toxin 2 / Q000633:toxicity*; D013921:Thrombocytopenia / Q000209:etiology; D014511:Uremia / Q000209:etiology
D015850:Interleukin-6; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2