Inhibitory Effect of Macrolides on Interleukin-8 Secretion from Nasal Epithelial Cells

The efficacy of long-term low-dose macrolide administration in the treatment of chronic sinusitis patients was evaluated. Ten patients with non-allergic chronic sinusitis were given 150mg of roxithromycin per day orally without any other treatment. The number of neutrophils in nasal smears was estimated using a grading scale. The neutrophil chemotactic activity and the interleukin-8 (IL-8) level of the nasal discharge were measured by the Boyden chamber method and by enzyme immunoassay, respectively. In addition, the patients underwent CT scan of paranasal sinuses before and after the treatment, and the percentage of aeration (%aeration) of the sinuses was calculated using a public domain NIH image program. The number of neutrophils, neutrophil chemotactic activity and the IL-8 level were simultaneously reduced. The %aeration of the paranasal sinuses significantly increased after the treatment.The effect of macrolide antibiotics on IL-8 secretion from cultured human nasal epithelial cells was then examined. Nasal polyps were surgically obtained from chronic sinusitis patients and treated with protease to liberate epithelial cells. The cells were primary-cultured, and secreted IL-8 in culture media was measured by enzyme immunoassay. IL-8 levels in the absence and presence of lipopolysaccharide were 172±25 and 372±83ng/106 cells/48h (mean±SEM), respectively. The secretion was significantly inhibited by 10-5M of erythromycin, clarithronmycin, roxithromycin and josamycin. Moreover, 10-6M erythromycin still showed the inhibitory effect while the same concentration of josamycin did not.These results suggest that long-term low-dose macrolide administration suppresses IL-8 secretion from nasal epithelial cells, and thereby blocks the vicious circle of continuous neutrophil exudation and the generation of chemotactic factors including IL-8 in the inflammatory sites of chronic sinusitis patients.