IL-10 DEFICIENCY MODULATES INFLAMATORY RESPONSE AND ANTI-INFLAMATORY MEDIATORS IN A MURINE MODEL OF HEMOLYTIC UREMIC SYNDROME (HUS)

GONZALO EZEQUIEL PINEDA,; BARBARA REARTE,; MARTÍN ISTURIZ,; MARLINA O. CORDOBA MORENO,; ROMINA J. FERNANDEZ-BRANDO, ; MARÍA VICTORIA RAMOS; CATALINA ALBA-SOTO, ; ANDREA BRUBALLA,; MARINA S. PALERMO,

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencia, 13-17 de Noviembre,; 2017

SAIC-SAIB-SAI-SAA-SAB-SAB-SAFE-SAFI-SAH-SAP

Hemolytic Uremic Syndrome is adisease triggered by Shiga toxin (Stx) characterized by hemolytic anemia,thrombocytopenia and renal failure. The concomitant inflammatory responsemediated mainly by neutrophils (PMN) is essential to HUS.Previously we demonstrated that mice lacking IL-10 (IL-10-/-)had a higher survival after Stx2 and a delayed neutrophilia compared to controlmice (wt). The aim of this work was to determine the mechanisms involved inIL-10-/- protection against Stx2.Before and 3h, 24h, 48h and 72hafter administration of 1LD100 of Stx2 e.v, IL-10-/-and wt mice were sacrificed. Plasma was collected to evaluate creatinine as anindicator of renal damage and corticosterone since IL-10 regulatesglucocorticoid synthesis at the level of the adrenal gland. Peripheral PMN weredetected as Ly6G+CD11b+ cells and CXCR2 and CD62Lexpression was analyzed by FACS.Even though creatinine levels(mg/dl) were increased at 72h in both strains, IL-10-/- showedreduced levels comparted to wt suggesting reduced renal damage (Wt0h:0.5±0.1; Wt72h: 1,4±0,1*; IL-10-/-0h: 0.4±0.1;IL-10-/-72h: 0.9±0.1*#, *<p0.05 vs 0h, #betweenstrains, n=10 per group). On the other hand, corticosterone levels (ng/ml) wereonly increased in IL-10-/- mice 3h after Stx2 (IL-10-/-0h:24,1±10,0; IL-10-/-3h: 337,9±56,0*# , *<p0.05vs 0h, #between strains, n=5 per group).Although there is a delayedneutrophilia in IL-10-/- mice (PMNx105/ml: Wt0h:11.5±0.1; Wt48h: 28.2±0.2*; Wt72h: 28.9±0.2*; IL-10-/-0h:14.7±0.1; IL-10-/-48h: 20.8±0.3#, IL-10-/-72h:25.1±0.2*, *<p0.05 vs 0h, #between strains, n=20 per group),there were no differences in CD62L and CXCR2 expression between strains afterStx2 treatment. This work show that Stx2 protection in IL-10-/- mice isassociated with reduced of renal damage and endogenous glucocorticoidcirculating levels, the most renowned anti-inflammatory factors.