Experimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia

Abstract Inflammation in chronic kidney disease (CKD) is mostly due to activation of the innate immune system, in which Interleukin-1 (IL-1) is a key player. Anemia of CKD may also be due to erythropoietin (EPO) resistance, clinically associated with inflammation. IL-1 receptor antagonist knockout (...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Inbar Bandach, Yael Segev, Daniel Landau
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0767ab32067442dda336ee71243999d1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0767ab32067442dda336ee71243999d1
record_format	dspace
spelling	oai:doaj.org-article:0767ab32067442dda336ee71243999d12021-12-02T17:04:53ZExperimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia10.1038/s41598-021-85778-22045-2322https://doaj.org/article/0767ab32067442dda336ee71243999d12021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85778-2https://doaj.org/toc/2045-2322Abstract Inflammation in chronic kidney disease (CKD) is mostly due to activation of the innate immune system, in which Interleukin-1 (IL-1) is a key player. Anemia of CKD may also be due to erythropoietin (EPO) resistance, clinically associated with inflammation. IL-1 receptor antagonist knockout (RaKO) mice show arthritis and excessive inflammation. Inhibition of IL-1 was shown to be beneficial in many inflammatory conditions, but its role in CKD and anemia is unknown. Here, we report that enhanced inflammation in RaKO mice with CKD provoked both higher degrees of renal insufficiency and anemia in comparison to wild-type CKD, in association with a downregulation of renal hypoxia inducible factor-2 (HIF2) as well as decreased bone marrow EPO-receptor (EPOR) and transferrin receptor (TFR). In contrast, administration of P2D7KK, an anti-IL1b monoclonal antibody, to CKD mice results in a lower grade of systemic inflammation, better renal function and blunted anemia. The latter was associated with upregulation of renal HIF-2α, bone marrow EPO-R and TFR. Altogether, this supports the key role of inflammation, and IL-1 particularly, in CKD progression and anemia. Novel treatments to reduce inflammation through this and other pathways, may improve renal function, attenuate the anemic state or increase the response to exogenous EPO.Inbar BandachYael SegevDaniel LandauNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Inbar Bandach Yael Segev Daniel Landau Experimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia
description	Abstract Inflammation in chronic kidney disease (CKD) is mostly due to activation of the innate immune system, in which Interleukin-1 (IL-1) is a key player. Anemia of CKD may also be due to erythropoietin (EPO) resistance, clinically associated with inflammation. IL-1 receptor antagonist knockout (RaKO) mice show arthritis and excessive inflammation. Inhibition of IL-1 was shown to be beneficial in many inflammatory conditions, but its role in CKD and anemia is unknown. Here, we report that enhanced inflammation in RaKO mice with CKD provoked both higher degrees of renal insufficiency and anemia in comparison to wild-type CKD, in association with a downregulation of renal hypoxia inducible factor-2 (HIF2) as well as decreased bone marrow EPO-receptor (EPOR) and transferrin receptor (TFR). In contrast, administration of P2D7KK, an anti-IL1b monoclonal antibody, to CKD mice results in a lower grade of systemic inflammation, better renal function and blunted anemia. The latter was associated with upregulation of renal HIF-2α, bone marrow EPO-R and TFR. Altogether, this supports the key role of inflammation, and IL-1 particularly, in CKD progression and anemia. Novel treatments to reduce inflammation through this and other pathways, may improve renal function, attenuate the anemic state or increase the response to exogenous EPO.
format	article
author	Inbar Bandach Yael Segev Daniel Landau
author_facet	Inbar Bandach Yael Segev Daniel Landau
author_sort	Inbar Bandach
title	Experimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia
title_short	Experimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia
title_full	Experimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia
title_fullStr	Experimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia
title_full_unstemmed	Experimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia
title_sort	experimental modulation of interleukin 1 shows its key role in chronic kidney disease progression and anemia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0767ab32067442dda336ee71243999d1
work_keys_str_mv	AT inbarbandach experimentalmodulationofinterleukin1showsitskeyroleinchronickidneydiseaseprogressionandanemia AT yaelsegev experimentalmodulationofinterleukin1showsitskeyroleinchronickidneydiseaseprogressionandanemia AT daniellandau experimentalmodulationofinterleukin1showsitskeyroleinchronickidneydiseaseprogressionandanemia
_version_	1718381771453628416

Experimental modulation of Interleukin 1 shows its key role in chronic kidney disease progression and anemia

Ejemplares similares