title: Anakinra reduces blood pressure and renal fibrosis in one kidney/DOCA/salt-induced hypertension.
abstract: To determine whether a clinically-utilised IL-1 receptor antagonist, anakinra, reduces renal inflammation, structural damage and blood pressure (BP) in mice with established hypertension.
  
  
  
  Hypertension was induced in male mice by uninephrectomy, deoxycorticosterone acetate (2.4mg/d,s.c.) and replacement of drinking water with saline (1K/DOCA/salt). Control mice received uninephrectomy, a placebo pellet and normal drinking water. 10days post-surgery, mice commenced treatment with anakinra (75mg/kg/d, i.p.) or vehicle (0.9% saline, i.p.) for 11days. Systolic BP was measured by tail cuff while qPCR, immunohistochemistry and flow cytometry were used to measure inflammatory markers, collagen and immune cell infiltration in the kidneys.
  
  
  
  By 10days post-surgery, 1K/DOCA/salt-treated mice displayed elevated systolic BP (148.3±2.4mmHg) compared to control mice (121.7±2.7mmHg; n=18, P<0.0001). The intervention with anakinra reduced BP in 1K/DOCA/salt-treated mice by ∼20mmHg (n=16, P<0.05), but had no effect in controls. In 1K/DOCA/salt-treated mice, anakinra modestly reduced (∼30%) renal expression of some (CCL5, CCL2; n=7-8; P<0.05) but not all (ICAM-1, IL-6) inflammatory markers, and had no effect on immune cell infiltration (n=7-8, P>0.05). Anakinra reduced renal collagen content (n=6, P<0.01) but paradoxically appeared to exacerbate the renal and glomerular hypertrophy (n=8-9, P<0.001) that accompanied 1K/DOCA/salt-induced hypertension.
  
  
  
  Despite its anti-hypertensive and renal anti-fibrotic actions, anakinra had minimal effects on inflammation and leukocyte infiltration in mice with 1K/DOCA/salt-induced hypertension. Future studies will assess whether the anti-hypertensive actions of anakinra are mediated by protective actions in other BP-regulating or salt-handling organs such as the arteries, skin and brain.
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Australia.
authors.forename: Yeong Hann
authors.initials: YH
authors.lastname: Ling
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Australia.
authors.forename: Shalini M
authors.initials: SM
authors.lastname: Krishnan
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Australia.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Chan
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Diep
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Australia.
authors.forename: Dorota
authors.initials: D
authors.lastname: Ferens
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Australia.
authors.forename: Jaye
authors.initials: J
authors.lastname: Chin-Dusting
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Australia.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Kemp-Harper
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Australia.
authors.forename: Chrishan S
authors.initials: CS
authors.lastname: Samuel
authors.affiliation: Department of Nephrology, Royal Melbourne Hospital, Parkville, Australia.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Hewitson
authors.affiliation: Institute of Innate Immunity, University Hospital Bonn, University of Bonn, Bonn, Germany; Department of Infectious Diseases and Immunology, University of Massachusetts Medical School,Worcester, Massachusetts, USA; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Eicke
authors.initials: E
authors.lastname: Latz
authors.affiliation: Hudson Institute of Medical Research, Clayton, Australia.
authors.forename: Ashley
authors.initials: A
authors.lastname: Mansell
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Australia; Department of Surgery, School of Clinical Sciences, Monash Health, Clayton, Australia.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
authors.affiliation: Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Australia; Department of Surgery, School of Clinical Sciences, Monash Health, Clayton, Australia. Electronic address: grant.drummond@monash.edu.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Drummond
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D064791:Desoxycorticosterone Acetate / Q000494:pharmacology; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D006977:Hypertension, Renal / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D017673:Sodium Chloride, Dietary; D018799:Intercellular Adhesion Molecule-1; D064791:Desoxycorticosterone Acetate
keywords: Anakinra; High blood pressure; IL-1β; Inflammasomes; Inflammation; Kidney