Clarithromycin suppresses proliferation of rat nasal epithelium exposed to endotoxin

A study was performed to elucidate the action of long-term macrolide therapy in chronic sinusitis. Clarithromycin (CAM) was administered orally once daily for 14 days. On the last 3 days, an endotoxin, lipopolysaccharide (LPS) was instilled intranasally. The extent of DNA synthesis acceleration was studied in both controls and pretreated animals by counting the number of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in the nasal transitional epithelium. Six hours after the final intranasal instillation of LPS, the number of BrdU-positive cells was significantly higher than control. Pretreatment with CAM for 2 weeks significantly inhibited this increase. Because similar results were obtained in neutrophil-depleted rats, LPS apparently promotes proliferation of the nasal epithelium in the absence of neutrophils: CAM-suppressed epithelial proliferation independently of the neutrophil count. Our results suggest that CAM inhibits LPS-induced increased rates of DNA synthesis by directly affecting the nasal epithelium. The mechanism by which macrolide therapy alleviates the signs and symptoms of chronic sinusitis might therefore involve suppression of inflammatory processes in the nasal and paranasal sinus epithelium.