title: Reverse kinetics of angiopoietin-2 and endotoxins in acute pyelonephritis: Implications for anti-inflammatory treatment?
abstract: Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFα). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang-2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFα production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells.
authors: 2nd Department of Urology, National and University of Athens, Medical School, Greece.
authors: Konstantinos
authors: K
authors: Safioleas
authors: 4th Department of Internal Medicine, National and University of Athens, Medical School, Greece. Electronic address: egiamarel@med.uoa.gr.
authors: Evangelos J
authors: EJ
authors: Giamarellos-Bourboulis
authors: 4th Department of Internal Medicine, National and University of Athens, Medical School, Greece.
authors: Dionyssia-Pinelopi
authors: DP
authors: Carrer
authors: 4th Department of Internal Medicine, National and University of Athens, Medical School, Greece.
authors: Aikaterini
authors: A
authors: Pistiki
authors: 4th Department of Internal Medicine, National and University of Athens, Medical School, Greece.
authors: Lambros
authors: L
authors: Sabracos
authors: 2nd Department of Urology, National and University of Athens, Medical School, Greece.
authors: Charalambos
authors: C
authors: Deliveliotis
authors: 2nd Department of Urology, National and University of Athens, Medical School, Greece.
authors: Michael
authors: M
authors: Chrisofos
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042702:Angiopoietin-2 / Q000097:blood* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004926:Escherichia coli / Q000502:physiology; D005260:Female; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000502:physiology; D011704:Pyelonephritis / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology; D011817:Rabbits; D018805:Sepsis / Q000097:blood / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D042702:Angiopoietin-2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha
keywords: Acute pyelonephritis; Angiopoietin-2; Endotoxins; Escherichia coli; Pseudomonas aeruginosa