title: Clarithromycin: immunomodulatory therapy of experimental sepsis and acute pyelonephritis by Escherichia coli.
abstract: The potency of clarithromycin as immunomodulator was assessed in an experimental model of sepsis based on acute pyelonephritis by susceptible Escherichia coli. 55 rabbits were utilized; 5 for preliminary pharmacokinetic study and 50 for treatment. The latter were divided into 5 groups of treatment, A: controls; B: clarithromycin pretreatment; C: amikacin pretreatment; D: clarithromycin treatment on presentation of pulmonary oedema; and E; amikacin treatment on presentation of pulmonary oedema. Survival was recorded; tumour necrosis factor-alpha (TNFalpha), and malondialdehyde (MDA) were estimated in serum; activities of caspase-3 in monocyte cytosolic extracts were studied; and bacterial counts made in various organs. Median survival of animals of groups A, B, C, D and E was 1.0, 21.0, 12.5, 2.0 and 5.0 d, respectively. TNFalpha and MDA and monocyte caspase-3 activity of group A increased over time; no increases were detected in groups B and C. Concentrations of MDA and activities of monocytic caspase-3 were decreased after administration of clarithromycin in group D, an effect not occurring in group E. Bacterial load was decreased in renal tissue of group D compared to group A. It is concluded that intravenous clarithromycin might constitute a promising immunomodulator in sepsis even in the advent of pulmonary oedema.
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece. giamarel@internet.gr
authors.forename: Evangelos
authors.initials: E
authors.lastname: Giamarellos-Bourboulis
authors.forename: Theodoros
authors.initials: T
authors.lastname: Adamis
authors.forename: Lambros
authors.initials: L
authors.lastname: Sabracos
authors.forename: Maria
authors.initials: M
authors.lastname: Raftogiannis
authors.forename: Fotini
authors.initials: F
authors.lastname: Baziaka
authors.forename: Thomas
authors.initials: T
authors.lastname: Tsaganos
authors.forename: Pantelis
authors.initials: P
authors.lastname: Koutoukas
authors.forename: Diamantis
authors.initials: D
authors.lastname: Plachouras
authors.forename: Panayotis
authors.initials: P
authors.lastname: Karayannacos
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000208:Acute Disease; D000583:Amikacin / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D017291:Clarithromycin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004926:Escherichia coli / Q000302:isolation & purification / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism; D007155:Immunologic Factors / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D011654:Pulmonary Edema / Q000188:drug therapy*; D011704:Pyelonephritis / Q000188:drug therapy* / Q000378:metabolism; D011817:Rabbits; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000583:Amikacin; D053148:Caspase 3; D020169:Caspases; D017291:Clarithromycin