PMID- 10531211 OWN - NLM STAT- MEDLINE DCOM- 19991116 LR - 20240407 IS - 0019-9567 (Print) IS - 1098-5522 (Electronic) IS - 0019-9567 (Linking) VI - 67 IP - 11 DP - 1999 Nov TI - Temporal sequence of pulmonary and systemic inflammatory responses to graded polymicrobial peritonitis in mice. PG - 5642-50 AB - 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 (C(st)) 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. C(st) 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. FAU - Stamme, C AU - Stamme C AD - Biochemical Pharmacology, University of Konstanz, University Hospital Hannover, Germany. FAU - Bundschuh, D S AU - Bundschuh DS FAU - Hartung, T AU - Hartung T FAU - Gebert, U AU - Gebert U FAU - Wollin, L AU - Wollin L FAU - Nusing, R AU - Nusing R FAU - Wendel, A AU - Wendel A FAU - Uhlig, S AU - Uhlig S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Cytokines) RN - 0 (Eicosanoids) RN - 0 (Proteins) RN - EC 1.11.1.7 (Peroxidase) SB - IM MH - Animals MH - Bacterial Infections/*immunology/physiopathology MH - Bronchoalveolar Lavage Fluid/chemistry MH - Cytokines/blood MH - Eicosanoids/blood MH - Gene Expression MH - Inflammation/*immunology/physiopathology MH - Lung Compliance MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Peritonitis/*immunology/physiopathology MH - Peroxidase/metabolism MH - Pneumonia/*immunology/physiopathology MH - Proteins/analysis PMC - PMC96937 EDAT- 1999/10/26 00:00 MHDA- 1999/10/26 00:01 PMCR- 1999/11/01 CRDT- 1999/10/26 00:00 PHST- 1999/10/26 00:00 [pubmed] PHST- 1999/10/26 00:01 [medline] PHST- 1999/10/26 00:00 [entrez] PHST- 1999/11/01 00:00 [pmc-release] AID - 0436 [pii] AID - 10.1128/IAI.67.11.5642-5650.1999 [doi] PST - ppublish SO - Infect Immun. 1999 Nov;67(11):5642-50. doi: 10.1128/IAI.67.11.5642-5650.1999.