The mechanism of macrolide therapy in chronic sinusitis patients is unclear. The authors studied the effect of macrolides on interleukin (IL)-8 secretion from cultured human nasal epithelial cells. Epithelial cells harvested from the nasal polyps of patients with chronic sinusitis were primary-cultured, and secreted IL-8 in culture media was measured by enzyme immunoassay. The cells secreted considerable amounts of IL-8 constitutively and in response to lipopolysaccharide. The secretion was significantly inhibited by 10(-5) M of erythromycin, clarithromycin, roxithromycin, and josamycin. 10(-6) M erythromycin still showed the inhibitory effect, whereas the same concentration of josamycin did not. These results indicate that macrolide antibiotics may act as an immunomodulator to reduce IL-8 in inflammatory sites and, at least partially, account for the clinically discrepant effects between 14- and 16-membered ring macrolides in long-term low-dose therapy for chronic sinusitis.