エンドトキシン吸入による気道杯細胞分泌反応に対するロキシスロマイシンの影響

Effect of Roxithromycin on Endotoxin-induced Hypersecretion of Airway Goblet Cells

　気道炎症病態における分泌亢進に対するマクロライド抗生剤の影響を明らかにする目的で，エンドトキシン（LPS）誘起性杯細胞分泌反応に対するロキシスロマイシン（RXM）の効果を検討した．モルモットにRXM（0.5〜10 mg／kg／day）を7日間経口投与し，LPS（5mg／kg）吸入の後，気管を摘出し杯細胞のmucus scoreを計測した．LPSは気管のmucusscoreを減少させ（572±61→94±20 AU,arbitrary units,p＜0.001），気管支肺胞洗浄液および気管粘膜上皮組織中の好中球数を増加させた．RXM投与群では上記の好中球集積は減少し，mucus scoreの変化も用量依存的に抑制された（最大抑制率：48.7±9.3％，p＜0.01）．一方，アモキシシリン，セファクロールはLPS誘起性好中球集積とmucus scoreの減少に対し無効であった．よって，マクロライドは好中球遊走に対する抑制作用を介し気道杯細胞分泌を抑制する可能性が示唆された．

Increased mucus glycoprotein secretion from airway goblet cells may play a significant role in the develop-ment of chronic airway infections such as diffuse pan-bronchiolitis and chronic bronchitis. To study the effect of macrolide on airway goblet cell secretion, we asses-sed the mucus score of guinea pig trachea, which is inversely related to the magnitude of mucus discharge. Inhaled LPS (5mg/kg) decreased mucus score and in-creased the number of neutrophils in bronchoalveolar lavage fluid. Oral administration of roxithromycin (0.5 -10mg/kg/day) for 7 days dose-dependently inhibited LPS-induced decrease in mucus score, with the maxi-mal inhibition being 48.7±9.3 % (p ＜ 0.01). This effect was accompanied by the inhibition of neutrophil accu-mulation into bronchoalveolar lavage fluid. On the other hand, amoxicillin and cefaclor had no effect on goblet cell secretion and recruitment of neutrophils. These results suggest that macrolide probably decreases goblet cell hypersecretion by inhibiting neutrophil accumulation in the airway.