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TNF-alpha increases sensitivity to LPS in chronically catheterized rats. Am J Physiol Heart Circ Physiol 2001 Jun;280(6):H2857-62

Date

05/18/2001

Pubmed ID

11356645

DOI

10.1152/ajpheart.2001.280.6.H2857

Scopus ID

2-s2.0-0034984913 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

Patients with severe trauma injury are transiently exposed to increased serum concentrations of tumor necrosis factor-alpha (TNF-alpha). These patients are susceptible to the development of multisystem organ failure (MSOF) triggered by subsequent exposure to bacterial toxins either via infection or increased intestinal permeability. We simulated the cytokine response of trauma by infusing 0.8 or 8.0 microg/kg of TNF-alpha (priming dose) into chronically catheterized rats. After 48 h, rats were challenged with endotoxin [lipopolysaccharide (LPS); 10 or 1,000 microg/kg]. Animals primed with either dose of TNF-alpha and then challenged with 1,000 microg/kg of LPS demonstrated significantly increased mortality, mean peak serum concentrations of interferon-gamma (IFN-gamma), and blood lactate concentrations (P < 0.05) compared with nonprimed animals. Mean peak serum concentrations of IFN-gamma and blood lactate concentrations were increased after challenge with 10 microg/kg of LPS only in animals primed with 8.0 microg/kg of TNF-alpha. Priming with TNF-alpha did not increase mortality after challenge with 10 microg/kg of LPS. These data suggest that both TNF-alpha release and the subsequent exposure to bacterial toxins mediate the pathophysiological progression from trauma to subsequent MSOF.

Author List

Goto M, Deriy LV, Chen YJ, Beno DW, Uhing MR, Jiyamapa-Serna VA, Kimura RE

Author

Michael R. Uhing MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Catheterization
Cytokines
Disease Models, Animal
Dose-Response Relationship, Drug
Infusions, Parenteral
Interferon-gamma
Lactic Acid
Lipopolysaccharides
Male
Metabolic Clearance Rate
Multiple Organ Failure
Rats
Rats, Sprague-Dawley
Survival Rate
Tumor Necrosis Factor-alpha