Low-dose and long-term treatment with macrolides antibiotics, including roxithromycin (RXM), is widely accepted, particulary in Japan, to favorably modify the clinical status of certain patients with chronic sinusitis. Although investigation of the mechanisms of its efficacy has suggested that it is not due to the antimicrobiological effects of the drugs, theprecise mechanisms are not well understood. The present study was designed to investigate the possible mechanisms of a low-dose and long-term RXM administration treatment.
Specific pathogen-free 5-week-old male BALB/c mice were divided into three groups, nontreated normal control, RXM-treated and RXM-nontreated group. Each group consisted with 20 mice, and they were maintained bacteria-, fungi-and parasite-free conditions throughout the experiments. The mice, which were treated with RXM at a single dose of 2.5 mg/kg once a day for various periods via stomach tube, were intratracheally instillated with 1.0 μg/ml LPS (0.1 ml), and aqueous lung extracts (ALE) were prepared 24 hrs after LPS instillation. The cytokine activities in ALE was measured by enzyme-linked immunosorbent assay in duplicate.
The results showed that long-term administration of RXM for a period of 7 and 12 weeks significantly (P <0.01) inhibited IL-1 β and TNF-α appearance in ALE induced by LPS instillation in comparison with those appearance in ALE from RXM-nontreated mice, whereas administration of RXM for 1 and 5 weeks scarcely affected IL-1 β and TNF-α appearance in ALE.
These results strongly suggested that the favorable effects of low-dose and long-term RXM administration treatment on chronic sinusitis might be explained partially by its inhibitory effects on inflammatory cytokine production.