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January 1990

Identification of a Novel Tumor Necrosis Factor αCachectin From the Livers of Burned and Infected Rats

Author Affiliations

From the Laboratory of Surgical Metabolism (Mr Keogh and Drs Fong, Marano, He, Barber, Minei, Lowry, and Moldawer) and the Division of Urology (Ms Seniuk and Dr Felsen), Department of Surgery, The New York (NY) Hospital–Cornell University Medical College.

Arch Surg. 1990;125(1):79-85. doi:10.1001/archsurg.1990.01410130085011

• Tumor necrosis factor α (TNF-α)/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-α/cachectin have only been episodically detected in hospitalized patients with life-threatening bacterial infections. In the present report, increased quantities of immune-reactive TNF-α/cachectin were recovered from the livers of rats 3 days following a lethal burn and infection. Two species of TNF-α/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-α/cachectin from the livers of lethally burned and infected rats represents a novel cell-associated form of the protein.

(Arch Surg. 1990;125:79-85)