RGD Reference Report - Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy. - Rat Genome Database

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Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy.

Authors: Andres-Hernando, A  Dursun, B  Altmann, C  Ahuja, N  He, Z  Bhargava, R  Edelstein, CE  Jani, A  Hoke, TS  Klein, C  Faubel, S 
Citation: Andres-Hernando A, etal., Nephrol Dial Transplant. 2012 Dec;27(12):4339-47. doi: 10.1093/ndt/gfs256. Epub 2012 Jul 9.
RGD ID: 7247739
Pubmed: PMID:22778179   (View Abstract at PubMed)
PMCID: PMC3520082   (View Article at PubMed Central)
DOI: DOI:10.1093/ndt/gfs256   (Journal Full-text)

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: Bilateral 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. RESULTS: Serum interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), IL-10, IL-1beta, 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-1beta and liver IL-6 and IL-10 were increased after bilateral nephrectomy. After IV injection, IL-6, CXCL1, IL-10 and IL-1beta 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acute kidney failure  ISOCcl11 (Mus musculus)7247739; 7247739protein:increased expression:kidneyRGD 
acute kidney failure  IEP 7247739protein:increased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl11  (C-C motif chemokine ligand 11)

Genes (Mus musculus)
Ccl11  (C-C motif chemokine ligand 11)

Genes (Homo sapiens)
CCL11  (C-C motif chemokine ligand 11)


Additional Information