title: Doxycycline attenuated lung injury by its biological effect apart from its antimicrobial function.
abstract: Antibiotics can have a biological effect apart from their anti-bacterial effect. We hypothesized that doxycycline could attenuate acute lung injury through its biological effect. Lipopolysaccharide or doxycycline-resistant Streptococcus pneumoniae was administered intratracheally into mice with the co-administration of doxycycline. Thereafter, the lung pathology, intraalveolar inflammatory cells, bacterial number, and matrix metalloproteinases were investigated. Matrix metalloproteinases, neutrophil migration, and alveolar destruction were induced by lipopolysaccharide. Doxycycline was thus found to improve all of these symptoms. In addition, an inhibitor of matrix metalloproteinases, CGS27023A, attenuated lipopolysaccharide-induced lung injury. Doxycycline also attenuated the lung injury induced by doxycycline-resistant S. pneumoniae and improved the mortality rate although the bacterial number in the lung did not change. Our data indicated that doxycycline could attenuate acute lung injury through a biological effect that was different from its antibiotic effect.
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka, Japan. fujita@kokyu.med.kyushu-u.ac.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujita
authors.forename: Eiji
authors.initials: E
authors.lastname: Harada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikegame
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ouchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Inoshima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006877:Hydroxamic Acids / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology; D013296:Streptococcus pneumoniae; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C097658:CGS 27023A; D006877:Hydroxamic Acids; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D011719:Pyrazines; D013449:Sulfonamides; D020782:Matrix Metalloproteinases; D004318:Doxycycline