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.


METHODS
Prospective 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.


METHODS
Animal research laboratory.


METHODS
Inbred 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).


RESULTS
The 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.


CONCLUSIONS
Organ-derived TNF-alpha plays a crucial role in the development of MODS in this murine model.
Burdon
D
D
Research Center Borstel, Medical Clinic, Technical University of Munich, Germany. dhburdon@aol.com
Tiedje
T
T
Pfeffer
K
K
Vollmer
E
E
Zabel
P
P
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*; D015054:Zymosan
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan