TISSUE TUMOR-NECROSIS-FACTOR MESSENGER-RNA EXPRESSION FOLLOWING CECALLIGATION AND PUNCTURE OR INTRAPERITONEAL INJECTION OF ENDOTOXIN

Tumor necrosis factor (TNF) has been implicated as a key mediator of t he septic response. Although very high serum levels of TNF are detecte d in animal models of endotoxemia or gram-negative bacteremia, human p atients with sepsis rarely have greatly elevated TNF serum levels. It has therefore been postulated that TNF may act in a paracrine fashion to cause local injury. In order to examine the role of locally produce d TNF in sepsis, we compared serum TNF levels and TNF messenger RNA (m RNA) expression in various tissues following cecal ligation and punctu re (CLP) or intraperitoneal injection of a sublethal dose of endotoxin . TNF mRNA expression was determined by the reverse transcription diff erential polymerase chain reaction using beta-actin as an internal sta ndard. Serum levels of TNF were threefold higher after endotoxin admin istration compared to CLP. TNF mRNA in peritoneal macrophages rose fou rfold after both endotoxin injection and CLP, with rapid return to nor mal in endotoxin-treated animals. There was a significant increase in TNF mRNA in the liver and lung, but not the spleen, during the first 2 4 hr after CLP. An increase in TNF mRNA was seen in all three tissues after injection of endotoxin. These results support the concept of loc ally produced TNF as a contributing factor in tissue damage and multip le organ failure during sepsis. (C) 1994 Academic Press, Inc.