PMID- 22778179 OWN - NLM STAT- MEDLINE DCOM- 20130712 LR - 20211021 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 27 IP - 12 DP - 2012 Dec TI - Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy. PG - 4339-47 LID - 10.1093/ndt/gfs256 [doi] AB - 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. FAU - Andres-Hernando, Ana AU - Andres-Hernando A AD - Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver, Aurora, CO, USA. Ana.AndresHernando@ucdenver.edu FAU - Dursun, Belda AU - Dursun B FAU - Altmann, Christopher AU - Altmann C FAU - Ahuja, Nilesh AU - Ahuja N FAU - He, Zhibin AU - He Z FAU - Bhargava, Rhea AU - Bhargava R FAU - Edelstein, Charles E AU - Edelstein CE FAU - Jani, Alkesh AU - Jani A FAU - Hoke, Thomas S AU - Hoke TS FAU - Klein, Christina AU - Klein C FAU - Faubel, Sarah AU - Faubel S LA - eng GR - R01 DK056851/DK/NIDDK NIH HHS/United States GR - R01 HL095363/HL/NHLBI NIH HHS/United States GR - R01 DK56851/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120709 PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Cytokines) SB - IM MH - Acute Kidney Injury/*metabolism MH - Animals MH - Cytokines/biosynthesis/*metabolism MH - Disease Models, Animal MH - Mice MH - Mice, Inbred C57BL MH - Nephrectomy PMC - PMC3520082 EDAT- 2012/07/11 06:00 MHDA- 2013/07/16 06:00 PMCR- 2013/12/01 CRDT- 2012/07/11 06:00 PHST- 2012/07/11 06:00 [entrez] PHST- 2012/07/11 06:00 [pubmed] PHST- 2013/07/16 06:00 [medline] PHST- 2013/12/01 00:00 [pmc-release] AID - gfs256 [pii] AID - 10.1093/ndt/gfs256 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2012 Dec;27(12):4339-47. doi: 10.1093/ndt/gfs256. Epub 2012 Jul 9.