EXPERIMENTAL CHRONIC PSEUDOMONAS-AERUGINOSA LUNG INFECTION IN RATS - NONSPECIFIC STIMULATION WITH LPS REDUCES LETHALITY AS EFFICIENTLY AS SPECIFIC IMMUNIZATION

In a rat model of chronic Pseudomonas aeruginosa lung infection mimick ing cystic fibrosis, we investigated the possibility of preventing chr onic lung inflammation or decreasing the progression of the infection. We compared the lethality pathology, bacterial clearance, and immunog enicity after stimulation of the non-specific defence mechanisms by Es cherichia coli lipopolysaccharide (LPS) or P. aeruginosa sonicate, or the acquired specific immune response by vaccination with the same bac terial antigens. One day prior to challenge with P. aeruginosa embedde d in alginate beads, rats were stimulated with either E. coli LPS or P . aeruginosa sonicate. Four and two weeks prior to challenge other rat s were vaccinated with either E. coli LPS or P. aeruginosa sonicate. C ontrols did not receive any stimulation or vaccination. The lethality after challenge was lower in rats stimulated with E. coli LPS (p=0.02) or vaccinated with P. aeruginosa sonicate (p=0.03) as compared to con trols. The histopathology of the surviving rats showed an acute inflam mation dominated by polymorphonuclear leukocytes (PMNs), but the offen ding bacteria were not completely eliminated in any group. The increas ed survival was probably due to earlier recruitment of PMNs most likel y mediated by either cytokines and other chemotactic factors (stimulat ed group) or the immune response in concert with the complement cascad e (vaccinated group). The results of the present and previous vaccinat ion studies show that it is possible to improve survival but not to pr event the chronic P. aeruginosa lung infection and inflammation caused by alginate-embedded bacteria.