Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy
Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy
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Abstract
BackgroundSerum 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.MethodsBilateral nephrectomy was used as a model of AKI to assess cytokine production independent of kidney cytokine production. Mononuclear phagocytes were depleted utilizing intravenous (IV) administration of liposome-encapsulated clodronate (LEC). Twenty-three serum cytokines were determined utilizing a multiplex cytokine kit. Proteins for cytokines were determined in the spleen and liver by enzyme-linked immunosorbent assay. Recombinant cytokines were injected by IV into mice with bilateral nephrectomy to determine the effect of absent kidney function on serum cytokine clearance.ResultsSerum interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), IL-10, IL-1ß, 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-1ß and liver IL-6 and IL-10 were increased after bilateral nephrectomy. After IV injection, IL-6, CXCL1, IL-10 and IL-1ß had a prolonged serum cytokine appearance in mice with bilateral nephrectomy versus sham operation.ConclusionsIncreased 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. © 2012 The Author.
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ORCID
Keywords
chemokines, CXCL1, cytokines, IL-6, mononuclear phagocytes, clodronic acid, CXCL1 chemokine, eotaxin, interleukin 10, interleukin 12p40, interleukin 1beta, interleukin 5, interleukin 6, monocyte chemotactic protein 1, RANTES, recombinant cytokine, acute kidney failure, animal experiment, animal model, animal tissue, article, blood sampling, controlled study, cytokine production, enzyme activation, enzyme activity, enzyme metabolism, kidney function, liver, mononuclear phagocyte, mouse, nephrectomy, nonhuman, priority journal, protein analysis, protein blood level, protein expression, protein function, spleen, Acute Kidney Injury, Animals, Cytokines, Disease Models, Animal, Mice, Mice, Inbred C57BL, Nephrectomy, interleukin 1beta, chemokines, Inbred C57BL, Nephrectomy, Mice, nephrectomy, kidney function, recombinant cytokine, article, protein function, Acute Kidney Injury, CXCL1, enzyme activity, priority journal, cytokine production, Cytokines, blood sampling, monocyte chemotactic protein 1, mononuclear phagocytes, animal experiment, 610, interleukin 6, interleukin 5, CXCL1 chemokine, liver, animal tissue, RANTES, acute kidney failure, Animals, controlled study, eotaxin, protein expression, mouse, IL-6, nonhuman, Animal, animal model, interleukin 12p40, enzyme activation, mononuclear phagocyte, cytokines, enzyme metabolism, Mice, Inbred C57BL, Disease Models, Animal, clodronic acid, protein analysis, protein blood level, Disease Models, spleen, interleukin 10
Fields of Science
0302 clinical medicine, 03 medical and health sciences
Citation
WoS Q
Scopus Q
OpenCitations Citation Count
108
Volume
27
Issue
12
Start Page
4339
End Page
4347
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