Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Surgery, Transplantation, azithromycin, ischemia reperfusion injury, lung donor, lung inflammation, lung transplantation, BRONCHIOLITIS OBLITERANS SYNDROME, TERM AZITHROMYCIN, RAT LUNG, TRANSPLANTATION, MACROLIDES, THERAPY, PHARMACOKINETICS, INTERLEUKIN-8, CYCLOSPORINE, NEUTROPHILS, Animals, Azithromycin, Bronchoalveolar Lavage Fluid, Chemokines, Cytokines, Dinoprost, Female, Inflammation, Interleukin-1beta, Interleukin-6, Leukocyte Count, Lung, Mice, Neutrophils, Oxidative Stress, Reperfusion Injury, 1103 Clinical Sciences, 3202 Clinical sciences

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.