Absence of interleukin-10 reduces progression of shiga toxin-induced hemolytic uremic syndrome

Abstract

Hemolytic Uremic Syndrome, a disease triggered by Shiga toxin (Stx), is characterized by hemolytic anemia, thrombocytopenia and renal failure. The inflammatory response mediated by neutrophils (PMN) and monocytes is essential to HUS onset. Still, the role of anti-inflammatory cytokines is less clear. The deficiency of IL-10, an anti-inflammatory cytokine, leads to severe pathology in bacterial infections but also to beneficial effects in models of sterile injury. The aim of this work was to analyze the role of IL-10 during HUS. Control and IL-10 lacking mice (IL-10-/-) were intravenously injected with Stx2 and survival rate was evaluated. PMN and circulating and renal pro- and anti-inflammatory factors were analyzed by FACS and ELISA respectively. IL-10-/- miceshowed a higher survival associated with lower renal damage reflected by reduced plasma urea and creatinine levels than control mice. Circulating PMN increased at 72 h in both mouse strains accompanied by an upregulation of CD11b in control mice. In parallel, renal PMN were significantly increased only in control mice after toxin. Plasma TNF-α, IL-6 and corticosterone levels were higher increased in IL-10-/- than control mice. Simultaneously renal TNF-α raised constantly but was accompanied by increased TGF-β levels in IL-10-/- mice. These results demonstrate that the profile of circulating and renal cytokines after Stx2 differed between strains suggesting that balance of these factors could participate in renal protection. We conclude that IL-10 absence has a protective role in an experimental model of HUS by reducing PMN recruitment into kidney and renal damage, and increasing mice survival.

Assessment of interleukin-10 promoter variant (−1082A/G) and cytokine production in patients with hemolytic uremic syndrome

“…Based on this, IL-10 could be considered not only a protective factor that regulates inflammation but also a detrimental factor that contributes to pathological changes leading to end-stage kidney diseases (18). In the context of HUS, it has been recently reported that the absence of IL-10 limits kidney damage in an experimental model induced by Stx (50).…”