IL-1β Receptor Antagonist Reduces Inflammation in Hemodialysis Patients

Hung, Adriana M.; Ellis, Charles D.; Shintani, Ayumi; Booker, Cindy; İkizler, T. Alp

doi:10.1681/asn.2010070760

Cited by 112 publications

(91 citation statements)

References 41 publications

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“…Of interest, IL1b is elevated in patients on maintenance hemodialysis and may contribute to the chronic inflammation noted in this population. Preliminary studies have examined the feasibility of targeted inhibition of IL-1 in patients on chronic hemodialysis, with additional studies ongoing (66).…”

Section: Specific Cytokine Inhibitionmentioning

confidence: 99%

Immunosuppressive Medications

Wiseman¹

2016

Clinical Journal of the American Society of Nephrology

202

165

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Immunosuppressive agents are commonly used in the nephrologist's practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist.

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Section: Specific Cytokine Inhibitionmentioning

confidence: 99%

Immunosuppressive Medications

Wiseman¹

2016

Clinical Journal of the American Society of Nephrology

202

165

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“…101 A first interventional study showed that anakinra can significantly improve C-reactive protein, IL-6, and serum albumin levels in patients on hemodialysis. 102 These data create hopes that blocking IL-1-driven systemic inflammation could improve nutritional status and body wasting, and eventually dampen accelerated cardiovascular disease in ESRD. 103 A trial with monoclonal anti-IL-1b IgG gevokizumab in diabetic kidney disease is ongoing.…”

Section: Il-1-related Drugs and Clinical Datamentioning

confidence: 99%

Of Inflammasomes and Alarmins: IL-1β and IL-1α in Kidney Disease

Anders

2016

JASN

204

152

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Kidney injury implies danger signaling and a response by the immune system. The inflammasome is a central danger recognition platform that triggers local and systemic inflammation. In immune cells, inflammasome activation causes the release of mature IL-1b and of the alarmin IL-1a. Dying cells release IL-1a also, independently of the inflammasome. Both IL-1a and IL-1b ligate the same IL-1 receptor (IL-1R) that is present on nearly all cells inside and outside the kidney, further amplifying cytokine and chemokine release. Thus, the inflammasome-IL-1a/IL-b-IL-1R system is a central element of kidney inflammation and the systemic consequences. Seminal discoveries of recent years have expanded this central paradigm of inflammation. This review gives an overview of arising concepts of inflammasome and IL-1a/b regulation in renal cells and in experimental kidney disease models. There is a pipeline of compounds that can interfere with the inflammasome-IL-1a/IL-b-IL-1R system, ranging from recently described small molecule inhibitors of NLRP3, a component of the inflammasome complex, to regulatory agency-approved IL-1-neutralizing biologic drugs. Based on strong theoretic and experimental rationale, the potential therapeutic benefits of using such compounds to block the inflammasome-IL-1a/IL-b-IL-1R system in kidney disease should be further explored.

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“…7 IL-1β is a proinflammatory cytokine that participates in human and experimental renal diseases. [8][9][10][11] Initial studies in the model of anti-Thy-1 nephritis demonstrated that IL-1β receptor blockade reduced glomerular macrophage accumulation. 8 More recently in an experimental model of type II diabetes the IL-1β receptor antagonist, anakinra, presented protective effects, 12 showing the involvement of this cytokine in renal inflammation.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II, via angiotensin receptor type 1/nuclear factor-κB activation, causes a synergistic effect on interleukin-1-β-induced inflammatory responses in cultured mesangial cells

Alique

Sánchez-López

Rayego‐Mateos

et al. 2014

J Renin Angiotensin Aldosterone Syst

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Introduction: The nuclear factor-κB (NF-κB) is an important regulator of the inflammatory response. Angiotensin II (Ang II) activates the NF-κB pathway linked to renal inflammation. Although both AT1 and AT2 receptors are involved in Ang II-mediated NF-κB activation, the biological processes mediated by each receptor are not fully characterized. Interleukin-1β (IL-1β) is an important macrophage-derived cytokine that regulates immune and inflammatory processes, activating intracellular pathways shared with Ang II, including the NF-κB. Materials and methods: In vitro studies were done in primary cultured rat mesangial cells. NF-κB pathway was evaluated by phosphorylated levels of p65/IκB and DNA binding activity. The Ang II receptor subtype was determined by pretreatment with AT1 and AT2 antagonists. Results: In mesangial cells the simultaneous presence of Ang II and IL-1β caused a synergistic activation of the NF-κB pathway and a marked upregulation of proinflammatory factors under NF-κB control, including monocyte chemoattractant protein-1. The AT1, but not AT2, antagonist abolished the synergistic effect on NF-κB activation and proinflammatory genes caused by coincubation of Ang II and IL-1β. Conclusions: These data indicates that Ang II, via AT1/NF-κB pathway activation, cooperates with IL-β to increase the inflammatory response in mesangial cellsThis work was supported by grants from the Instituto de Salud Carlos III (ISCIIIRETIC REDinREN RD06/0016, RD12/0021, PI11/01854), Comunidad de Madrid (Fibroteam S2010/BMD- 2321, S2010/BMD-2378), and Research Institute Queen Sophia (IRSIN). Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to AO. MA and ESL are supported by a ‘Sara Borrell’ postdoctoral contract from Instituto de Salud Carlos III (CD10/00347 and CD09/00066, respectively

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IL-1β Receptor Antagonist Reduces Inflammation in Hemodialysis Patients

Cited by 112 publications

References 41 publications

Immunosuppressive Medications

Immunosuppressive Medications

Of Inflammasomes and Alarmins: IL-1β and IL-1α in Kidney Disease

Angiotensin II, via angiotensin receptor type 1/nuclear factor-κB activation, causes a synergistic effect on interleukin-1-β-induced inflammatory responses in cultured mesangial cells

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