title: Immunomodulatory intervention with interferon-γ in Escherichia coli pyelonephritis.
abstract: OBJECTIVE
  We investigated the efficacy of recombinant human interferon-γ in experimental pyelonephritis due to Escherichia coli.
  
  
  METHODS
  Pyelonephritis was induced by intrapelvic inoculation of bacteria after ureteral ligation in 38 rabbits assigned to 1 of 3 groups, including group 1-16 controls, group 2-14 rabbits treated with intravenous recombinant human interferon-γ and group 3-8 rabbits treated with intravenous recombinant human interferon-γ plus amikacin. Bacterial counts, cytokines and malondialdehyde were measured in blood. Peripheral blood mononuclear cells were isolated to measure TNFα transcripts, cytokine stimulation and apoptosis. Survival was recorded, and the tissue bacterial load and myeloperoxidase activity were measured after sacrifice.
  
  
  RESULTS
  The mortality rate in groups 1, 2 and 3 was 66.7%, 25% and 12.5%, respectively. The circulating bacterial count and tissue bacterial load were less in group 2 than in group 1. Circulating malondialdehyde negatively correlated with the bacterial load of the spleen. Although the number of TNFα transcripts in circulating peripheral blood mononuclear cells did not differ, peripheral blood mononuclear cells isolated from group 2 at 48 hours produced much greater concentrations of tumor necrosis factor-α after stimulation with Pam3Cys. In parallel, the apoptosis rate of circulating monocytes was increased in group 2 at 48 hours. Lung myeloperoxidase activity at 24 hours, serving as indirect evidence of neutrophil infiltration, was decreased in group 2.
  
  
  CONCLUSIONS
  Recombinant human interferon-γ administration prolonged survival in rabbits with experimental E. coli urosepsis. Its action was probably related to increased bacterial phagocytosis after modulation of oxidant status and reversal of monocyte immunoparalysis.
authors.affiliation: 2nd Department of Urology, University of Athens Medical School, Athens, Greece. Electronic address: katsarismud8@yahoo.com.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Katsaris
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Adamis
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Pistiki
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Dionyssia-Pinelopi
authors.initials: DP
authors.lastname: Carrer
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Galani
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Labros
authors.initials: L
authors.lastname: Sabracos
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Dionyssia-Irini
authors.initials: DI
authors.lastname: Droggiti
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Marianna
authors.initials: M
authors.lastname: Georgitsi
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Damoraki
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.affiliation: 2nd Department of Urology, University of Athens Medical School, Athens, Greece.
authors.forename: Michael
authors.initials: M
authors.lastname: Chrisofos
mesh_terms: D000818:Animals; D004927:Escherichia coli Infections / Q000188:drug therapy*; D056747:Immunomodulation; D007371:Interferon-gamma / Q000627:therapeutic use*; D008297:Male; D011704:Pyelonephritis / Q000188:drug therapy* / Q000382:microbiology*; D011817:Rabbits
chemical_list: C573415:IFNG protein, human; D007371:Interferon-gamma
keywords: Escherichia coli; immunomodulation; interferon-gamma; kidney; pyelonephritis