Abstract | BACKGROUND: Serum cytokines are increased in patients with acute kidney injury (AKI) and predict increased mortality. It is widely assumed that increased renal production of cytokines is the source of increased serum cytokines; the role of extra-renal cytokine production and impaired renal cytokine clearance is less well studied. We hypothesized that cytokine production in AKI was mononuclear phagocyte dependent, independent of production by the kidneys, and that serum cytokine clearance would be impaired in AKI. METHODS: RESULTS: Serum interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), IL-10, IL-1β, monocyte chemotactic protein 1 (MCP-1), IL-5 and eotaxin were increased in the serum of mice after bilateral nephrectomy and were reduced with LEC. Serum IL-12p40 and regulated upon activation, normal T-cell expressed, and secreted ( RANTES) were increased after bilateral nephrectomy and were further increased with LEC. Spleen IL-6, CXCL1, IL-10 and IL-1β and liver IL-6 and IL-10 were increased after bilateral nephrectomy. After IV injection, IL-6, CXCL1, IL-10 and IL-1β had a prolonged serum cytokine appearance in mice with bilateral nephrectomy versus sham operation. CONCLUSIONS: Increased mononuclear phagocyte production and impaired renal clearance contribute to serum cytokine accumulation in AKI, independent of kidney injury. The effect of AKI on cytokine production and clearance may contribute to the increased mortality of patients with AKI.
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Authors | Ana Andres-Hernando, Belda Dursun, Christopher Altmann, Nilesh Ahuja, Zhibin He, Rhea Bhargava, Charles E Edelstein, Alkesh Jani, Thomas S Hoke, Christina Klein, Sarah Faubel |
Journal | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
(Nephrol Dial Transplant)
Vol. 27
Issue 12
Pg. 4339-47
(Dec 2012)
ISSN: 1460-2385 [Electronic] England |
PMID | 22778179
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Acute Kidney Injury
(metabolism)
- Animals
- Cytokines
(biosynthesis, metabolism)
- Disease Models, Animal
- Mice
- Mice, Inbred C57BL
- Nephrectomy
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