title: Azithromycin reduces airway inflammation in a murine model of lung ischaemia reperfusion injury.
abstract: Clinical studies revealed that azithromycin reduces airway neutrophilia during chronic rejection after lung transplantation. Our aim was to investigate the possible effect of azithromycin on ischaemia-reperfusion injury. Azithromycin or water was administered to mice every other day during 2 weeks (n = 6/group). On the 14th day, the left lung was clamped to induce ischaemia (90 min). In two additional groups, animals underwent the same protocol, followed by 4 h of reperfusion. Two control groups were included with thoracotomy only. Inflammatory parameters and oxidative stress were measured in broncho-alveolar lavage of the left lung. Leukocytes, lymphocytes, neutrophils, 8-isoprostane and IL-1beta levels after ischaemia and reperfusion were significantly reduced in mice treated with azithromycin. There was a trend towards lower IL-6 and KC levels. A significant correlation was seen between 8-isoprostanes and neutrophils (Pearson r = 0.72; P = 0.0086), IL-6 (Pearson r = 0.84; P = 0.0006), KC (Pearson r = 0.88; P = 0.0002) and IL-1beta (Pearson r = 0.62; P = 0.0326). We conclude (i) that azithromycin reduces inflammation and oxidative stress in our IRI model, and (ii) that oxidative stress is correlated with the number of neutrophils and IL-6, KC and IL-1beta levels after ischaemia and reperfusion. Azithromycin should be further investigated as a novel drug to prevent lung ischaemia-reperfusion injury.
authors.affiliation: Laboratory of Experimental Thoracic Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Geudens
authors.forename: Lien
authors.initials: L
authors.lastname: Timmermans
authors.forename: Hadewijch
authors.initials: H
authors.lastname: Vanhooren
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
authors.forename: Robin
authors.initials: R
authors.lastname: Vos
authors.forename: Caroline
authors.initials: C
authors.lastname: Van De Wauwer
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.forename: Toni
authors.initials: T
authors.lastname: Lerut
authors.forename: Dirk E M
authors.initials: DE
authors.lastname: Van Raemdonck
mesh_terms: D000818:Animals; D017963:Azithromycin / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D015237:Dinoprost / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D007249:Inflammation; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000098:blood supply / Q000473:pathology*; D051379:Mice; D009504:Neutrophils; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000473:pathology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; C075750:8-epi-prostaglandin F2alpha; D017963:Azithromycin; D015237:Dinoprost