• D Burdon, T Tiedje, K Pfeffer, E Vollmer, and P Zabel.
• Research Center Borstel, Medical Clinic, Technical University of Munich, Germany. dhburdon@aol.com
• Crit. Care Med. 2000 Jun 1;28(6):1962-7.

ObjectiveTo elucidate the role of tumor necrosis factor (TNF) in the development of multiple organ dysfunction syndrome (MODS) after zymosan-induced peritonitis in mice.DesignProspective controlled laboratory study on zymosan-induced generalized inflammation in mice. Over < or =28 days, a single intraperitoneal administration of zymosan induced a three-phase illness in C57BL mice, rendering them very ill with MODS-like symptoms from day 7 onward. Additionally, the same experiment was performed on C57BL/6 TNF-Rc-p55 knockout mice to elucidate the role of TNF and its receptor p55.SettingAnimal research laboratory.SubjectsInbred C57BL mice and C57BL p55-/- mice received a single sterile intraperitoneal injection of zymosan suspended in paraffin oil (0.75 mg/g of body weight).Measurements And Main ResultsThe animals were monitored for survival, condition, and body weight for < or =28 days. At 3, 7, 14, and 28 days after zymosan administration, bronchoalveolar lavage was performed and lungs and livers were extracted for isolation of RNA and histopathologic evaluation. Reverse-transcriptase-polymerase chain reaction was performed to quantify TNF-alpha messenger RNA (mRNA) in the respective organs. Both animal strains went through initial shock with a high mortality rate during the first 3 days. The C57BL mice developed MODS with typical symptoms and histopathologic results correlating with excessive TNF-alpha mRNA expression from day 7 onward. In contrast, no disease, histopathologic changes, nor TNF-alpha mRNA expression in liver or lung was found within the TNF-Rc-p55-/- mice.ConclusionOrgan-derived TNF-alpha plays a crucial role in the development of MODS in this murine model.

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