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The inflammatory response in blood and in remote organs following acute kidney injury.
APMIS. 2014 May; 122(5):399-404.A

Abstract

In patients with acute kidney injury (AKI) mortality remains high, despite the fact that the patients are treated with continuous renal replacement therapy. The interaction between the kidney and the immune system might explain the high mortality observed in AKI. In order to elucidate the interaction between the kidney and immune system we developed a two-hit model of AKI and endotoxemia. Our hypothesis was that ischemia/reperfusion (I/R) of the kidney simultaneously with endotoxemia would generate a more extensive inflammatory response compared to I/R of the hind legs. Our expectation was that elevated levels of cytokines would be found in both blood and in organs distant to the kidneys. Forty mice were divided into five groups. The mice were subjected to the following operations: A: Sham only, no lipopolysaccharide (LPS); B: I/R of both kidneys + LPS; C: LPS only; D: Nephrectomy + LPS; E: I/R of both hind legs + LPS. In groups B and E, I/R times were identical. All mice were kept alive for 24 h and then sacrificed. Levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were measured in the blood. The activity of myeloperoxidase (MPO) in lungs, kidneys, and liver was evaluated as an indirect measurement of accumulation of granulocytes. In this study, significantly higher amount of IL-6 and IL-10 in the plasma was observed following renal I/R compared to hind leg I/R. The elevated levels of cytokine in plasma were observed following nephrectomy and endotoxemia. The neutrophil infiltration of distant organs measured by the levels of MPO in the lung and liver also showed a significantly higher level in renal I/R compared to hind leg I/R. Renal I/R is associated with a more pronounced inflammatory response in blood and distant organs. The high cytokine levels measured following nephrectomy might be explained by compromised elimination of cytokines by the kidney in AKI.

Authors+Show Affiliations

Department of Anesthesiology and Intensive Care Medicine, Odense University Hospital, Odense, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24033773

Citation

Brøchner, Anne Craveiro, et al. "The Inflammatory Response in Blood and in Remote Organs Following Acute Kidney Injury." APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica, vol. 122, no. 5, 2014, pp. 399-404.
Brøchner AC, Dagnaes-Hansen F, Højberg-Holm J, et al. The inflammatory response in blood and in remote organs following acute kidney injury. APMIS. 2014;122(5):399-404.
Brøchner, A. C., Dagnaes-Hansen, F., Højberg-Holm, J., & Toft, P. (2014). The inflammatory response in blood and in remote organs following acute kidney injury. APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica, 122(5), 399-404. https://doi.org/10.1111/apm.12157
Brøchner AC, et al. The Inflammatory Response in Blood and in Remote Organs Following Acute Kidney Injury. APMIS. 2014;122(5):399-404. PubMed PMID: 24033773.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The inflammatory response in blood and in remote organs following acute kidney injury. AU - Brøchner,Anne Craveiro, AU - Dagnaes-Hansen,Frederik, AU - Højberg-Holm,Jimmy, AU - Toft,Palle, Y1 - 2013/09/06/ PY - 2013/06/14/received PY - 2013/07/04/accepted PY - 2013/9/17/entrez PY - 2013/9/17/pubmed PY - 2014/6/10/medline KW - Ischemia/reperfusion KW - LPS KW - endotoxemia KW - kidney KW - mice KW - two-hit model SP - 399 EP - 404 JF - APMIS : acta pathologica, microbiologica, et immunologica Scandinavica JO - APMIS VL - 122 IS - 5 N2 - In patients with acute kidney injury (AKI) mortality remains high, despite the fact that the patients are treated with continuous renal replacement therapy. The interaction between the kidney and the immune system might explain the high mortality observed in AKI. In order to elucidate the interaction between the kidney and immune system we developed a two-hit model of AKI and endotoxemia. Our hypothesis was that ischemia/reperfusion (I/R) of the kidney simultaneously with endotoxemia would generate a more extensive inflammatory response compared to I/R of the hind legs. Our expectation was that elevated levels of cytokines would be found in both blood and in organs distant to the kidneys. Forty mice were divided into five groups. The mice were subjected to the following operations: A: Sham only, no lipopolysaccharide (LPS); B: I/R of both kidneys + LPS; C: LPS only; D: Nephrectomy + LPS; E: I/R of both hind legs + LPS. In groups B and E, I/R times were identical. All mice were kept alive for 24 h and then sacrificed. Levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were measured in the blood. The activity of myeloperoxidase (MPO) in lungs, kidneys, and liver was evaluated as an indirect measurement of accumulation of granulocytes. In this study, significantly higher amount of IL-6 and IL-10 in the plasma was observed following renal I/R compared to hind leg I/R. The elevated levels of cytokine in plasma were observed following nephrectomy and endotoxemia. The neutrophil infiltration of distant organs measured by the levels of MPO in the lung and liver also showed a significantly higher level in renal I/R compared to hind leg I/R. Renal I/R is associated with a more pronounced inflammatory response in blood and distant organs. The high cytokine levels measured following nephrectomy might be explained by compromised elimination of cytokines by the kidney in AKI. SN - 1600-0463 UR - https://www.unboundmedicine.com/medline/citation/24033773/The_inflammatory_response_in_blood_and_in_remote_organs_following_acute_kidney_injury_ L2 - https://doi.org/10.1111/apm.12157 DB - PRIME DP - Unbound Medicine ER -