Azithromycin reduces airway inflammation in a murine model of lung ischaemia reperfusion injury.
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.
Geudens
Nele
N
Laboratory of Experimental Thoracic Surgery, Katholieke Universiteit Leuven, Leuven, Belgium.
Timmermans
Lien
L
Vanhooren
Hadewijch
H
Vanaudenaerde
Bart M
BM
Vos
Robin
R
Van De Wauwer
Caroline
C
Verleden
Geert M
GM
Verbeken
Erik
E
Lerut
Toni
T
Van Raemdonck
Dirk E M
DE
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*
D018925:Chemokines; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; C075750:8-epi-prostaglandin F2alpha; D017963:Azithromycin; D015237:Dinoprost