EFFECT OF ERYTHROMYCIN ON ENDOTOXIN-INDUCED MICROVASCULAR LEAKAGE IN THE RAT TRACHEA AND LUNGS

To determine whether the macrolide antibiotic erythromycin prevents mi crovascular leakage produced by lipopolysaccharide (LPS), we studied t racheae and lungs of pathogen-free rats. Tracheal vasular permeability and neutrophil recruitment were assessed by the percent area occupied by Monastral blue-labeled blood vessels and by myeloperoxidase-contai ning granulocytes, respectively, in tracheal whole mounts. Pulmonary m icrovascular leakage was evaluated by lung wet-to-dry (W/D) weight rat io. Inhalation of Escherichia coli LPS (5 mg/kg) caused time-dependent increases in tracheal vascular permeability, neutrophil influx, and l ung W/D ratio. These responses were inhibited by pretreatment with ora l erythromycin, but not by ampicillin or cefaclor, in a dose-dependent manner: erythromycin at 10 mg/kg daily for 1 wk reduced the area dens ity of Monastral blue-labeled vessels from 6.7 +/- 1.2 to 1.4 +/- 0.3% (p < 0.01), the number of neutrophils (from 365 +/- 51 to 149 +/- 30 cells/mm(2), p < 0.01), and lung W/D weight ratio (from 6.76 +/- 0.30 to 5.39 +/- 0.21, p < 0.01). This inhibitory effect of erythromycin wa s abolished by depletion of circulating neutrophils with cyclophospham ide. These results suggest that LPS causes acute lung injury, microvas cular leakage, and neutrophil recruitment in the trachea, and that ery thromycin protects against these changes, probably by acting on neutro phils.