Leukocytosis (mostly neutrophils) is thought to be one prognostic factor for the pathogenesis of hemolytic uremic syndrome (HUS) due to entrohemorrhagic E. coli.
The author speculated that neutrophils are activated and cells play a role for the pathogenesis of HUS due to entrohemorrhagic E. coli.
Thus, the author investigated 1) the increased levels of proinflammatory cytokines, which are especially involved in the activation of PMN, in plasmas from patients, and 2) the possibility of the activation of granulocytes by vero toxins.
The results are as follows:
1) Plasma levels of cytokines and other mediators: The levels of three groups; Group A (patients with HUS), Group B (patients hospitalized with diarrhea but not HUS), and Group C (outpatients with diarrhea), were compared. High levels of IL-8 and PMN-elastase were found in Group A and B, but the levels were higher in Group A. Other proinflammatory cytokines were also found especially in Group A. Endotoxin levels were within cut-off value, even insevere cases. Procalcitonin, as an indictor of severe bacterial infection, was found in Group A.
2) Activation of granulocytes with vero toxins: Vcro toxin (VT 1) activated granulocytes to produce proinflammatory cytokines (IL-6, IL-8, TNF-α, and IL-8) and to express the adhesion molecules (CD11b and CD18; Mac-I). VT2 also activated granulocytes to produce cytokines and to express the adhesion molecules. The potency of VT2 was superior to VT1. CD77 (Gb3) antigen was found to be expressed on granulocytes.
These results suggest that the activation of granulocytes plays a role in the pathogenesis of HUS and is a vehicle to deliver vero toxins to organs.