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

• Published in: Archives of surgery (Chicago. 1960) Vol. 125; no. 1; p. 79
• Main Authors: Keogh, C, Fong, Y, Marano, M A, Seniuk, S, He, W, Barber, A, Minei, J P, Felsen, D, Lowry, S F, Moldawer, L L
• Format: Journal Article
• Language: English
• Published: United States 01-01-1990
• Subjects: Animals; Blotting, Western; Burns - metabolism; Electrophoresis, Polyacrylamide Gel; Female; Kupffer Cells - metabolism; Liver - analysis; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Molecular Weight; Pseudomonas aeruginosa; Pseudomonas Infections - metabolism; Rats; Rats, Inbred Strains; Sodium Dodecyl Sulfate; Tumor Necrosis Factor-alpha - isolation & purification
• ISSN: 0004-0010
• DOI: 10.1001/archsurg.1990.01410130085011

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.