Inhibitory effects of 14-membered ring macrolide antibiotics on bleomycin-induced acute lung injury.
14-membered ring macrolides have been reported to have anti-inflammatory effects and to decrease neutrophil infiltration into the airways in chronic lower respiratory tract diseases. This study investigated the potential inhibitory effects of macrolide antibiotics on bleomycin-induced acute lung injury. Four drugs were studied: two 14-membered ring macrolides, clarithromycin (CAM) and roxithromycin (RXM); a 15-membered ring macrolide, azithromycin (AZM); and a 16-membered ring macrolide, josamycin (JM). Their effects were compared with macrolide untreated, pretreated, and post-treated groups. An acute lung injury was inhibited by pretreatment with CAM or RXM, which significantly ameliorated the bleomycin-induced increases in the total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluids and the wet lung weight. The pretreatment with CAM or RXM also suppressed inflammatory cell infiltration and interstitial lung edema in the histopathological study. These inhibitory effects were associated with a decreased KC concentration in the BAL fluid and a decreased number of apoptotic cells in the lungs. Posttreatment with CAM or RXM had no marked inhibitory effects. Pretreatment with AZM was much less effective, and JM showed no inhibitory effects. These findings suggest that 14-membered ring macrolides have different effects on inflammatory lung disease than 15- and 16-membered ring macrolides and may be therapeutic agents for acute lung injury and pulmonary fibrosis.
Department of Medicine, Saga Medical School, Nabeshima, Japan.
M
M
Kawashima
J
J
yatsunami
Y
Y
Fukuno
M
M
Nagata
M
M
Tominaga
S
S
Hayashi
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D017963:Azithromycin / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D001761:Bleomycin / Q000009:adverse effects*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D017291:Clarithromycin / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006133:Growth Substances / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D036341:Intercellular Signaling Peptides and Proteins; D015570:Josamycin / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011654:Pulmonary Edema / Q000188:drug therapy; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000188:drug therapy*; D015575:Roxithromycin / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D013997:Time Factors; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D001761:Bleomycin; D015575:Roxithromycin; D017963:Azithromycin; D017291:Clarithromycin; D015570:Josamycin