The role of tumor necrosis factor in the development of multiple organ failure in a murine model

Objective: To elucidate the role of tumor necrosis factor (TNF) in the development of multiple organ dysfunction syndrome (MODS) after zymosan-induced peritonitis in mice. Design: Prospective controlled laboratory study on zymosan-induced generalized inflammation in mice. Over less than or equal to 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. Setting: Animal research laboratory. Subjects: Inbred G57BL 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 Results: The animals were monitored for survival, condition, and body weight for less than or equal to 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. Conclusion: Organ-derived TNF-alpha plays a crucial role in the development of MODS in this murine model.