Effect of antibiotic therapy on the inflammatory responses during streptococcal pneumonia in emphysematous mice

Abstract

Background and objective: Bacterial infection is one of the most important causes of acute exacerbation of respiratory failure in patients with chronic obstructive pulmonary disease (COPD). There were few studies evaluating the effects of early intervention by antibiotic on respiratory bacterial infection in COPD subjects. We investigated the effect of early intervention by respiratory quinolone antibiotic on the systemic inflammatory responses induced by streptococcal pneumonia using a mouse model of experimental emphysema. Methods: Experimental pulmonary emphysema was developed by a single intratracheal instillation of porcine pancreatic elastase in ICR mice. Three weeks later, lethal doses of Streptococcus pneumoniae were intratracheally inoculated, followed by oral administration of 50 mg/kg body weight of Grepafloxacin (GPFX) every day from a day after tracheal inoculation. Results: While all emphysematous mice without GPFX treatment died within 8 days, all emphysematous mice with GPFX treatment survived. Seventy two hrs after infection, serum levels of tumor necrosis factor alpha, chemokine (C-X-C motif) ligand 1, and CXCL2 (Macrophage inflammatory protein-2) in emphysematous mice with antibiotic therapy were significantly lower than those without therapy. Conclusions: Thus, the early intervention using a respiratory quinolone antibiotic prevents emphysematous mice with pneumonia from severe systemic inflammation, and rescues these mice from death. These results suggest that early intervention using a respiratory quinolone may improve the outcome of the exacerbated COPD patients.