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Infection and Immunity, November 1999, p. 5642-5650, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Temporal Sequence of Pulmonary and Systemic Inflammatory Responses to Graded Polymicrobial Peritonitis in Mice

Cordula Stamme,1,2 Daniela Sophie Bundschuh,1 Thomas Hartung,1 Ulla Gebert,1 Lutz Wollin,1 Rolf Nüsing,3 Albrecht Wendel,1 and Stefan Uhlig1,*

Biochemical Pharmacology, University of Konstanz, Konstanz,1 Medical Center of Pediatrics, University Hospital Marburg, Marburg,3 and Department of Anesthesiology, University Hospital Hannover, Hannover,2 Germany

Received 26 March 1999/Returned for modification 25 May 1999/Accepted 18 August 1999

The lungs are the remote organ most commonly affected in human peritonitis. The major goals of this study were to define the dose- and time-dependent relationship between graded septic peritonitis and systemic and pulmonary inflammatory responses in mice. BALB/c mice were treated with intraperitoneal polymicrobial inoculi and sacrificed at 3, 12, and 24 h. The treatment protocol resulted in distinct groups of animals with respect to mortality rate, kinetics, and concentrations of a broad spectrum of pro- and anti-inflammatory endogenous mediators, intrapulmonary bacterial accumulation, and static lung compliance. In sublethally infected mice, pulmonary bacterial proliferation 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 infection exclusively. At 3 h, MCP-1, gamma interferon, and TNF were detected in extracts of pulmonary tissue or in bronchoalveolar lavage (BAL) fluid. Static lung compliance (Cst) was transiently decreased at 12 h. In contrast, in lethally infected mice pulmonary bacterial proliferation was not contained. Concentrations of MCP-1, G-CSF, and TNF in plasma were maximal at 24 h, as were pulmonary MCP-1 levels. Lung myeloperoxidase activity was increased at 3, 12, and 24 h. Cst was reduced after 3 h and did not reach control values at 24 h. Pulmonary cyclooxygenase-2 mRNA and eicosanoids in BAL fluid and plasma were elevated at 3 and 24 h. This study shows that polymicrobial peritonitis in mice leads to dose-dependent systemic and pulmonary inflammation accompanied by a decrease in lung compliance.

* Corresponding author. Mailing address: Research Center Borstel, Division Pulmonary Pharmacology, Parkallee 22, 23845 Borstel, Germany. Phone: 49-4537-188478. Fax: 49-4537-188778. E-mail: SUhlig{at}fz-borstel.de.

Infection and Immunity, November 1999, p. 5642-5650, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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