Nosocomial pneumonia is a feared complication in the critically ill patient. Aspiration pneumonitis is frequently complicated by infections. The objective of this study was to determine the influence of aspiration pneumonitis on the host response to a common nosocomial respiratory pathogen.
Controlled, in vivo laboratory study.
Research laboratory of a health sciences university.
Female C57Bl/6 mice.
Mice received hydrochloric acid or saline intratracheally followed 16 hrs later by Klebsiella pneumoniae.
Hydrochloric acid induced a mild aspiration pneumonitis. Nonetheless, hydrochloric acid aspiration resulted in a markedly increased inflammatory response in the lung on infection with K. pneumoniae. This enhanced inflammatory reaction was accompanied by a greatly increased outgrowth of K. pneumoniae in lungs of mice previously exposed to hydrochloric acid. Preexisting aspiration pneumonitis also triggered mouse lungs in vivo and alveolar macrophages ex vivo for enhanced release of proinflammatory mediators on stimulation with Klebsiella lipopolysaccharide. Inhibition of tumor necrosis factor-α resulted in an increased inflammatory reaction and enhanced bacterial outgrowth in mice with primary K. pneumoniae pneumonia, whereas it had no effect in mice with preexisting aspiration pneumonitis.
These data indicate a) that aspiration pneumonitis renders the host more susceptible to respiratory tract infection with K. pneumoniae, concurrently priming the lung for an exaggerated inflammatory response; and b) that although tumor necrosis factor-α plays a major role in the host response to primary infection, it does not affect lung inflammation or defense after aspiration pneumonitis.
From the Divisions of Experimental Internal Medicine (DJvW, SK, CvV, AFdV, TvdP), Pathology (SF), and Infectious Diseases (TvdP), Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and the Department of Surgery (WAB), University of Limburg, Maastricht, the Netherlands
Supported by the Academic Medical Center, Amsterdam, Netherlands; and by Celltech, Slough, UK, which donated TN3.