| Abstract | Tumor necrosis factor (TNF), a macrophage product released in response to endotoxin and other stimuli, has been shown to be a central mediator of endotoxin or septic shock. However, its highly conserved and wide-ranging physiological effects suggest that it may also be an essential cytokine in the host defense against acute bacterial infection or sepsis. A single nontoxic dose of human recombinant TNF administered intravenously 24 h prior to a lethal infusion of Escherichia coli lipopolysaccharide (LPS) completely prevented acute LPS-induced hypotension, ameliorated tissue injury in the lungs and liver, and improved survival in male Fisher 344 rats. The protective effects of TNF were dose dependent and required a 24-h pretreatment interval. After the infusion of LPS, animals in both groups (TNF-treated animals and saline-pretreated controls) initially appeared acutely ill and had a similar severe metabolic acidosis, indicating that TNF did not inactivate or prevent the toxic effects of LPS. Twelve hours after the administration of TNF, the gene for manganous superoxide dismutase, a mitochondrial enzyme which scavenges toxic reactive oxygen species and is induced during conditions which generate a free radical stress, was expressed in liver tissue, suggesting that the induction of manganous superoxide dismutase may be an important in vivo protective mechanism against cellular injury during lethal endotoxemia. |
| Authors | H R Alexander, G M Doherty, M I Block, P J Kragel, J C Jensen, H N Langstein, E Walker, J A Norton
(Affiliation: Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.)
|
| Journal | Infection and immunity
(Infect Immun)
Vol. 59
Issue 11
Pg. 3889-94
(Nov 1991)
ISSN: 0019-9567 UNITED STATES |
| PMID | 1937748
(Publication Type: Journal Article)
|
| Chemical References |
- Lipopolysaccharides
- RNA, Messenger
- Tumor Necrosis Factor-alpha
- Superoxide Dismutase
|
| Topics |
- Animals
- Blotting, Northern
- Enzyme Induction
- Gene Expression
- Lipopolysaccharides
(toxicity)
- RNA, Messenger
(genetics)
- Rats
- Rats, Inbred F344
- Shock, Septic
(pathology, physiopathology, prevention & control)
- Superoxide Dismutase
(genetics)
- Time Factors
- Tumor Necrosis Factor-alpha
(therapeutic use)
|
