title: Circulating IL-6 upregulates IL-10 production in splenic CD4+T cells and limits acute kidney injury-induced lung inflammation.
abstract: Although it is well established that acute kidney injury (AKI) is a proinflammatory state, little is known about the endogenous counter-inflammatory response. IL-6 is traditionally considered a pro-inflammatory cytokine that is elevated in the serum in both human and murine AKI. However, IL-6 is known to have anti-inflammatory effects. Here we sought to investigate the role of IL-6 in the counter-inflammatory response after AKI, particularly in regard to the anti-inflammatory cytokine IL-10. Ischemic AKI was induced by bilateral renal pedicle clamping. IL-10-deficient mice had increased systemic and lung inflammation after AKI, demonstrating the role of IL-10 in limiting inflammation after AKI. We then sought to determine whether IL-6 mediates IL-10 production. Wild-type mice with AKI had a marked upregulation of splenic IL-10 that was absent in IL-6-deficient mice with AKI. In vitro, addition of IL-6 to splenocytes increased IL-10 production in CD4+T cells, B cells, and macrophages. In vivo, CD4-deficient mice with AKI had reduced splenic IL-10 and increased lung myeloperoxidase activity. Thus, IL-6 directly increases IL-10 production and participates in the counter-inflammatory response after AKI.
authors.affiliation: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Andres-Hernando
authors.affiliation: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Kayo
authors.initials: K
authors.lastname: Okamura
authors.affiliation: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Rhea
authors.initials: R
authors.lastname: Bhargava
authors.affiliation: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Kiekhaefer
authors.affiliation: Department of Pediatrics and Bioengineering, University of Colorado, Aurora, Colorado, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Soranno
authors.affiliation: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Kirkbride-Romeo
authors.affiliation: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA; Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.
authors.forename: Hyo-Wook
authors.initials: HW
authors.lastname: Gil
authors.affiliation: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Altmann
authors.affiliation: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA. Electronic address: sarah.faubel@ucdenver.edu.
authors.forename: Sarah
authors.initials: S
authors.lastname: Faubel
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015704:CD4 Antigens; C556062:IL10 protein, mouse; D015850:Interleukin-6; C577686:interleukin-6, mouse; D016753:Interleukin-10; D009195:Peroxidase
keywords: acute kidney injury; cytokines; ischemic reperfusion