Absence of interleukin-10 reduces progression of shiga toxin-induced hemolytic uremic syndrome
| Autor: | María Florencia Todero, María Victoria Ramos, Catalina D. Alba-Soto, Gonzalo Ezequiel Pineda, Alan Mauro Bernal, Andrea Cecilia Bruballa, Marina S. Palermo, Elsa Zotta, Bárbara Rearte, Martín A. Isturiz, Romina Jimena Fernandez-Brando |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Hemolytic anemia Neutrophils medicine.medical_treatment 030106 microbiology Kidney urologic and male genital diseases medicine.disease_cause Shiga Toxin 2 03 medical and health sciences chemistry.chemical_compound Transforming Growth Factor beta medicine Animals Mice Knockout Mice Inbred BALB C Creatinine biology Interleukin-6 Tumor Necrosis Factor-alpha Toxin business.industry Shiga toxin General Medicine medicine.disease Interleukin-10 Survival Rate Interleukin 10 030104 developmental biology Cytokine medicine.anatomical_structure chemistry Hemolytic-Uremic Syndrome Immunology biology.protein Tumor necrosis factor alpha Corticosterone business |
| Zdroj: | Clinical Science. 135:575-588 |
| ISSN: | 1470-8736 0143-5221 |
| DOI: | 10.1042/cs20200468 |
| Popis: | Hemolytic Uremic Syndrome (HUS), a disease triggered by Shiga toxin (Stx), is characterized by hemolytic anemia, thrombocytopenia and renal failure. The inflammatory response mediated by polymorphonuclear neutrophils (PMNs) 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 Stx type 2 (Stx2) and survival rate was evaluated. PMN and circulating and renal pro- and anti-inflammatory factors were analyzed by FACS and enzyme-linked immunosorbent assay (ELISA) respectively. IL-10−/− mice showed 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 up-regulation 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. |
| Databáze: | OpenAIRE |
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