CHARACTERIZATION OF S. PNEUMONIAE PNEUMONIA-INDUCED MULTIPLE ORGAN DYSFUNCTION SYNDROME: AN EXPERIMENTAL MOUSE MODEL OF GRAM-POSITIVE SEPSIS

Streptococcus pneumoniae, a gram-positive bacteria, is the most common cause of community-acquired pneumonia. It is a common cause of septic shock with multiple organ dysfunction syndrome (MODS) resulting in significant mortality. Gram-positive mouse models of sepsis with MODS are required to examine mechanisms of immune responses in severe sepsis. To assess whether lung infection due to S. pneumoniae in a nonventilated mouse model can induce multiple organ dysfunction. S. pneumoniae, SPIN 15814 strain, harvested at log phase, was injected intratracheally in C57BL/6 mice at OD600 between 0.35 and 0.63. A dose of bacteria at OD600 = 0.63 conferred approximately 30% mortality in 36 h. Lung pneumonia was assessed by histology, lung myeloperoxidase activity, and lung bacterial load; intestinal epithelial barrier integrity was assessed by measuring blood-to-lumen clearance of Cr-51-EDTA; renal function was assessed by measuring plasma creatinine and urea; and myocardiac function was assessed using an isolated perfused mouse heart model. S. pneumoniae-induced pneumonia resulted in neutrophil infiltration into the lungs and increased lung bacterial load. Although relatively few bacteria gained access to the blood stream, the pneumonia was accompanied by increased intestinal epithelial barrier permeability, increased plasma creatinine, and decreased cardiac output and stroke volume. These data clearly show that intratracheal S. pneumoniae induced not only pneumonia but also MODS, despite the fact that few organisms gain access to the blood stream. This model can be used as a good gram-positive model of sepsis and MODS for further studies.