Temporal sequence of pulmonary and systemic inflammatory responses to graded polymicrobial peritonitis in mice

The lungs are the remote organ most commonly affected in human peritonitis. The major goals of this study were to define tbe dose- and time-dependent relationship between graded septic peritonitis and systemic and pulmonary i nflammatory responses in mice. BALB/c mice were treated with intraperitonea l polymicrobial inoculi and sacrificed at 3, 12, and 24 h. The treatment pr otocol resulted in distinct groups of animals with respect to mortality rat e, kinetics, and concentrations of a broad spectrum of pro- and anti-inflam matory endogenous mediators, intrapulmonary bacterial accumulation, and sta tic lung compliance. In sublethally infected mice, pulmonary bacterial prol iferation was controlled. Levels of monocyte chemoattractant protein-1 (MCP -1), interleukin-10, interleukin-6, granulocyte colony-stimulating factor ( G-CSF), and tumor necrosis factor (TNF) in plasma were elevated 3 h after i nfection exclusively. At 3 h, MCP-1, gamma interferon, and TNF were detecte d in extracts of pulmonary tissue or in bronchoalveolar lavage (BAL) fluid. Static lung compliance (C-st) was transiently decreased at 12 h. In contra st, in lethally infected mice pulmonary bacterial proliferation was not con tained. Concentrations of MCP-1, G-CSF, and TNF in plasma were maximal at 2 4 h, as mere pulmonary MCP-1 levels. Lung myeloperoxidase activity was incr eased at 3, 12, and 24 h C-st was reduced after 3 h and did not reach contr ol values at 24 h. Pulmonary cyclooxygenase-2 mRNA and eicosanoids in BAL f luid and plasma were elevated at 3 and 24 h. This study shows that polymicr obial peritonitis in mice leads to dose-dependent systemic and pulmonary in flammation accompanied by a decrease in lung compliance.