Effects of macrolides on interleukin-8 secretion from human nasal epithelial cells.
Low-dose, long-term macrolide treatment has recently been reported to be very effective in patients with chronic airway diseases. We examined the in vivo and in vitro effects of 14-membered macrolide antibiotics erythromycin (EM) and clarithromycin (CAM) on interleukin (IL)-8 secretion from human nasal epithelial cells. Fifteen patients with chronic sinusitis received macrolide treatment (CAM 400 mg/day) for 1 to 3 months. The number of infiltrated neutrophils and IL-8 concentrations in the nasal discharges of these patients decreased significantly at 1 to 2 months after the treatment. In vitro effects of EM and CAM on IL-8 secretion were examined in nasal epithelial cells cultured at the air-liquid interface. After 14-day culture in the air-liquid interface, macrolide antibiotics were added in medium for 24 h. EM and CAM at concentrations of 10(-4) M did not affect spontaneous secretions or IL-1 beta-induced secretions of IL-8 either apically or basolaterally. When cells were preincubated with 10(-4) M CAM for 7 days, the IL-1 beta-induced secretion of IL-8 decreased significantly. However, no difference was observed between the effects of 10(-4) M CAM and 10(-4) M josamycin, a 16-membered macrolide. These results suggest that macrolide treatment inhibits neutrophil infiltration and IL-8 secretion in nasal epithelium in vivo and that these clinical effects depend on a mechanism other than the direct action of macrolide on nasal epithelial cells.
Fujita
K
K
Department of Otorhinolaryngology, Mie University School of Medicine, Japan.
Shimizu
T
T
Majima
Y
Y
Sakakura
Y
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002648:Child; D002908:Chronic Disease; D017291:Clarithromycin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004917:Erythromycin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D009666:Nose / Q000166:cytology; D012852:Sinusitis / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D007375:Interleukin-1; D016209:Interleukin-8; D004917:Erythromycin; D017291:Clarithromycin