IL-10 DEFICENCY PROTECTS RENAL DAMAGE IN A MURINE MODEL OF HEMOLYTIC UREMIC SYNDROME

PINEDA, G; FERNÁNDEZ BRANDO, ROMINA J; BÁRBARA REARTE; ISTURIZ, MARTIN A; ALBA-SOTO, C; PALERMO, MARINA S; RAMOS, M. VICTORIA

Buenos Aires

Congreso; IV LASID Meeting LXIII Argentinean Society for Immunology Meeting II French-Argentinean Immunology Meeting; 2015

LASID-FAIC-SAI

Background:Hemolytic Uremic Syndrome (HUS), a vascular disease characterized by nephropathy, is caused by enterohemorraghic-producing-Shiga-toxins (Stx)bacteria. The aim of the work was to determine the role of IL-10 in HUSevolution. Methods:  Mice lacking IL-10 (IL-10-/-) and control mice were injected i.v. with 1LD100 Stx2. Before and after 2, 48 and 72h Stx2, mice were bled to perform polymorphonuclear leukocytes(PMN) counts, urea and cytokine evaluation. Results: IL-10-/- mice had a higher survival rate toStx2 than controls (%survivors:44 and 0, median survival: 120h  and 96h, respectively, *p<0.005). Ureaincrease, main marker of kidney damage, at 72h after Stx2 was significantly reduced in IL-10-/- mice comparedto controls (urea (mg%):IL-10-/-=168.7±39.9*;control=342.3±39.6,*p<0.05, n=5). Since PMN are implicated in endothelialdamage induced by Stx2 we analyzed the % PMN before and after Stx2 in bothstrains. In basal condition both strains showed similar %PMN in blood but after Stx2 injection, meanwhile the increase in %PMN was seen at 48h post-Stx2 incontrols, it was delayed at 72h in IL10-/- mice (%PMN Basal/Stx2=IL-10-/-(72h)= (22.2±3.0/60.2±5.9*, control (48h)=15.9±2.8/58.2±2.9*, *p<0.01vs basal. The TNF-alfa  increased 2h post-Stx2 in plasma only in IL-10-/- mice (IL-10-/-=90.2±3.1*,control=2.1±1.2,n=5) pg/ml, *p<0.05. Conclusions:IL10-/- mice showed an increase in TNF-alfa levels, and eventhough this cytokine is an inflammatory factor which potentiates Stx toxicity,  these  mice are less sensitive to toxin effects. Our data suggest that in absence of IL-10, others anti-inflamatory mechanisms are involved in mediating protection to Stx2 in the mouse model of HUS.