title: Clinical and immunoregulatory effects of roxithromycin therapy for chronic respiratory tract infection.
abstract: The clinical and immunoregulatory effects of long-term macrolide antibiotic therapy for patients with chronic lower respiratory tract infections (CLRTI) were investigated. Clinical parameters and neutrophil chemotactic mediators in the epithelial lining fluid (ELF) of CLRTI patients (n = 10) were examined before and after 3 months oral administration of roxithromycin (RXM). The in vitro effects of RXM were also examined on the release of these mediators from alveolar macrophages (AM) and neutrophils. Arterial oxygen tension (p<0.05), vital capacity (VC) (p<0.001), %VC (p<0.05) and forced expiratory volume in one second (p<0.01) were improved after RXM treatment, but airway bacteria were not eradicated. Among the mediators, the levels of interleukin (IL)-8, neutrophil elastase (NE) and leukotriene B4 (LTB4) were higher in ELF than in plasma of CLRTI patients and they decreased after RXM treatment (n = 7, p<0.05 for each). RXM concentrations were significantly increased in the bronchoalveolar lavage cells of the treated patients. In in vitro experiments, RXM showed inhibitory effects on IL-8 release from AM and neutrophils. In conclusion, interleukin-8, neutrophil elastase and leukotriene B4 contribute to the neutrophilic inflammation in the airways of chronic lower respiratory tract infection patients and the clinical effects of roxithromycin may, in part, be attributable to the suppression of excess release of the chemotactic mediators from inflammatory cells.
authors.affiliation: Dept. of Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Fujishima
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Ohkubo
authors.forename: K
authors.initials: K
authors.lastname: Soejima
authors.forename: Y
authors.initials: Y
authors.lastname: Waki
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Urano
authors.forename: F
authors.initials: F
authors.lastname: Sakamaki
authors.forename: S
authors.initials: S
authors.lastname: Tasaka
authors.forename: A
authors.initials: A
authors.lastname: Ishizaka
authors.forename: M
authors.initials: M
authors.lastname: Kanazawa
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001987:Bronchiectasis / Q000503:physiopathology; D001988:Bronchiolitis / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002630:Chemotactic Factors / Q000378:metabolism; D002908:Chronic Disease; D005541:Forced Expiratory Volume; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000032:analysis; D019272:Leukocyte Elastase / Q000032:analysis; D007975:Leukotriene B4 / Q000032:analysis; D016676:Macrophages, Alveolar / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D015575:Roxithromycin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014797:Vital Capacity
chemical_list: D000900:Anti-Bacterial Agents; D002630:Chemotactic Factors; D016209:Interleukin-8; D007975:Leukotriene B4; D015575:Roxithromycin; D019272:Leukocyte Elastase; D010100:Oxygen