Please use this identifier to cite or link to this item: https://hdl.handle.net/11499/8397
Title: Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy
Authors: Andres-Hernando, A.
Dursun, Belda
Altmann, C.
Ahuja, N.
He, Z.
Bhargava, R.
Edelstein, C.E.
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
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.
URI: https://hdl.handle.net/11499/8397
https://doi.org/10.1093/ndt/gfs256
ISSN: 0931-0509
Appears in Collections:PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Tıp Fakültesi Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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