Identification of a novel tumor necrosis factor alpha/cachectin from the livers of burned and infected rats

Tumor necrosis factor alpha (TNF-alpha)/cachectin is a monocyte/macrophage-derived cytokine implicated as a proximal mediator of many of the catastrophic host responses to infection or endotoxin. However, circulating levels of TNF-alpha/cachectin have only been episodically detected in hospitalized patients with life-threatening bacterial infections. In the present report, increased quantities of immune-reactive TNF-alpha/cachectin were recovered from the livers of rats 3 days following a lethal burn and infection. Two species of TNF-alpha/cachectin were detected, one of approximately 29 kd and the other 17 kd, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In murine peritoneal macrophages and rat Kupffer cells stimulated in vitro with endotoxin, a 29-kd cell-associated and 17-kd secreted form were also detected. We conclude that the increased appearance in vivo of a 29-kd form of TNF-alpha/cachectin from the livers of lethally burned and infected rats represents a novel cell-associated form of the protein.