Microbiological and inflammatory factors associated with the development of pneumococcal pneumonia

Pneumococcal pneumonia still is associated with a high mortality rate, desp ite appropriate antimicrobial therapy. Many gaps remain in the understandin g of the pathogenesis of this deadly infection. The microbial and inflammat ory events that characterize survival or death after intranasal inoculation of mice with an LD50 inoculum of Streptococcus pneumoniae were investigate d. Survival was associated with rapid bacterial clearance and low inflammat ion (surfactant and red blood cells in alveoli), but no neutrophil recruitm ent or lung tissue injury was noted. By contrast, death was preceded by str ong bacterial growth that peaked 48 h after the infection and was associate d with gradual increases in pulmonary levels of interleukin-6, macrophage i nflammatory protein (MIP)-1 alpha, MIP-2, monocyte chemoattractant protein- 1, KC, and neutrophil recruitment. The injection of tumor necrosis factor-a lpha or the addition of lipopolysaccharide or heat-killed S. pneumoniae to the inoculum enhanced early host response and survival. These observations may help develop appropriate markers of evolution of pneumonia, as well as new therapeutic strategies.