Doxycycline attenuated lung injury by its biological effect apart from its antimicrobial function

Pulm Pharmacol Ther. 2007;20(6):669-75. doi: 10.1016/j.pupt.2006.08.006. Epub 2006 Sep 14.


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.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Disease Models, Animal
  • Doxycycline / pharmacology*
  • Drug Resistance, Bacterial
  • Hydroxamic Acids / pharmacology
  • Immunologic Factors / pharmacology*
  • Inflammation / drug therapy*
  • Lipopolysaccharides
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Lung Diseases / drug therapy*
  • Lung Diseases / immunology
  • Lung Diseases / pathology
  • Matrix Metalloproteinases / drug effects
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology
  • Pyrazines / pharmacology
  • Streptococcus pneumoniae
  • Sulfonamides / pharmacology


  • Anti-Bacterial Agents
  • CGS 27023A
  • Hydroxamic Acids
  • Immunologic Factors
  • Lipopolysaccharides
  • Pyrazines
  • Sulfonamides
  • Matrix Metalloproteinases
  • Doxycycline