IL-10 DEFICIENCY MODULATES INFLAMMATORYRESPONSE AND ANTI-INFLAMMATORY MEDIATORS INA MURINE MODEL OF HEMOLYTIC UREMIC SYNDROME(HUS)?

PALERMO, MARINA S.; BRUBALLA, ANDREA; ALBA-SOTO, C; ISTURIZ, MARTIN A; BÁRBARA REARTE; PINEDA, G; RAMOS, MARIA VICTORIA; FERNANDEZ BRANDO, ROMINA; MARLINA CÓRDOBA MORENO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

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

Hemolytic Uremic Syndrome is a disease triggered by Shiga toxin(Stx) characterized by hemolytic anemia, thrombocytopenia and renalfailure. The concomitant inflammatory response mediated mainlyby neutrophils (PMN) is essential to HUS.Previously we demonstrated that mice lacking IL-10 (IL-10-/-) hada higher survival after Stx2 and a delayed neutrophilia compared tocontrol mice (wt). The aim of this work was to determine the mechanismsinvolved in IL-10-/- protection against Stx2.Before and 3h, 24h, 48h and 72h after administration of 1LD100 of Stx2 e.v, IL-10-/- and wt mice were sacrificed. Plasma was collectedto evaluate creatinine as an indicator of renal damage and corticosteronesince IL-10 regulates glucocorticoid synthesis at the level ofthe adrenal gland. Peripheral PMN were detected as Ly6G+CD11b+cells and CXCR2 and CD62L expression was analyzed by FACS.Even though creatinine levels (mg/dl) were increased at 72h inboth strains, IL-10-/- showed reduced levels comparted to wt suggestingreduced 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) were only increased in IL-10-/-mice 3h after Stx2 (IL-10-/-0h:24,1±10,0; IL-10-/-3h: 337,9±56,0*# , *<p0.05 vs 0h, #between strains,n=5 per group).Although there is a delayed neutrophilia 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 vs0h, #between strains, n=20 per group), there were no differencesin CD62L and CXCR2 expression between strains after Stx2 treatment.This work show that Stx2 protection in IL-10-/- mice is associatedwith reduced of renal damage and endogenous glucocorticoid circulatinglevels, the most renowned anti-inflammatory factors.