title: TNF-alpha increases sensitivity to LPS in chronically catheterized rats.
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.
authors.affiliation: Section of Neonatology, Department of Pediatrics, Rush Children's Hospital, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois 60612, USA.
authors.forename: M
authors.initials: M
authors.lastname: Goto
authors.forename: L V
authors.initials: LV
authors.lastname: Deriy
authors.forename: Y J
authors.initials: YJ
authors.lastname: Chen
authors.forename: D W
authors.initials: DW
authors.lastname: Beno
authors.forename: M R
authors.initials: MR
authors.lastname: Uhing
authors.forename: V A
authors.initials: VA
authors.lastname: Jiyamapa-Serna
authors.forename: R E
authors.initials: RE
authors.lastname: Kimura
mesh_terms: D000818:Animals; D002404:Catheterization; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007263:Infusions, Parenteral; D007371:Interferon-gamma / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009102:Multiple Organ Failure / Q000097:blood* / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D007371:Interferon-gamma