Silicosis is associated with increased susceptibility to pulmonary infection with the pathogen Mycobacterium tuberculosis. We hypothesized that in experimental silicosis (ESIL), pulmonary host defense to the facultative intracellular pathogen L. monocytogenes (LM) would also be impaired as the result of a relative decrease in Type 1 cytokine response. ESIL was induced in F344 rats by quartz inhalation. Controls were exposed to diluent air only. LM infections were induced by intratracheal instillation of 104 organisms. Rats were sacrificed at 3 and 7 days after instillation and numbers of viable LM were measured in left lung, lung-associated lymph node (LALN) and spleen. In addition, presence of mRNA for interferon-A, IL-2, IL-4, IL-1O, TNF-alpha,G3PDH, and beta-actin were assessed in lung and LALN by RT -PCR. ESIL was associated with markedly increased numbers of viable LM in LALN at day 3 (p<0.0l) and LALN, lung, and spleen at day 7 (p<0.01). ESIL was also associated with increased transcription in lung and LALN, relative to air controls, of interferon-A at days 3 and 7, and TNF-alpha at day 7. Levels of transcription of other cytokine genes were similar in ESIL and air groups. Thus, ESIL impairs host defense to pulmonary L. monocytogenes infection. Both pulmonary clearance -and dissemination of infection are affected. Furthermore, impaired host defense is not simply the result of a relative decrease in Type 1 cytokine response.
Animal-studies; Laboratory-animals; Statistical-analysis; Analytical-methods; Analytical-chemistry; Exposure-assessment; Toxicology; Toxins; Toxic-materials; Pulmonary-system-disorders; Pulmonary-disorders; Respiratory-system-disorders; Respiratory-irritants; Particulate-dust; Particulates; Dust-exposure; Dust-inhalation; Dust-particles; Airborne-dusts; Airborne-fibers; Airborne-particles; Silica-dusts; Silicates