Differential toxicity of inhaled gram-negative bacteria.

The toxicity by inhalation of various gram-negative bacteria, isolated from settings associated with inhalation disease, was studied by a variety of means. These microorganisms were not equally toxic. Citrobacter freundii aerosol challenges of rabbits provoked significant (up to fivefold) increases in plasma haptoglobin 24 to 48 h after inhalation. Other strains tested failed to provoke such statistically consistent increases. Measurements of C-reactive protein in these same animals did not lead to as reliable results, due to the variability of the responses. Mice responded differently to inhalation in that haptoglobin responses were either unaffected or depressed. When a strain of mice was used that exhibits more severe inflammatory responses to endotoxin (C3H/HeJ), C. freundii and Escherichia coli aerosols provoked significant haptoglobin increases. Free lung cell analyses demonstrated that the macrophage and neutrophil responses differed depending on the strain of bacteria used. Again, C. freundii induced the greatest responses. When murine B lymphocytes were stimulated with lipopolysaccharide preparations from different gram-negative bacteria, distinctly different dose-response curves were obtained. The types of responses obtained indicate that (i) brief inhalation of bacterial aerosols previously thought to be innocuous may lead to pulmonary inflammation, and (ii) that these bacteria differ in their toxicity, with C. freundii being the most toxic organism of the five studied.