Efficacy of anti-tumor necrosis factor polyclonal antibody on phosphoenolpyruvate carboxykinase expression in septic and endotoxemic rats.
We studied the protective effect of anti-tumor necrosis factor-alpha (anti-TNF) polyclonal antibody on phosphoenolpyruvate carboxykinase (PEPCK) expression in lipopolysaccharide-induced endotoxemia and peritonitis sepsis induced by cecal incision. At 3 h after intraperitoneal lipopolysaccharide injection, levels of serum glucose, liver glycogen, and PEPCK expression were decreased and serum TNF was elevated. In contrast, 3 h after cecal incision, levels of serum glucose, serum TNF, and PEPCK expression were elevated. At 6 h after cecal incision (terminal sepsis), serum TNF remained elevated and levels of serum glucose, liver glycogen, and PEPCK expression were decreased. Circulating TNF was not detected in septic and endotoxemic rats pretreated with anti-TNF. Passive immunization with rat anti-TNF antibody restored PEPCK expression in early endotoxemia and sepsis (3 h), but not in terminal sepsis (6 h). Anti-TNF failed to reverse sepsis-induced hypoglycemia and hyperglycemia, suggesting that besides TNF, some other mediators are involved in glucose dyshomeostasis.
Chang
C K
CK
Department of Surgery, Finch University of Health Sciences, Chicago Medical School at Mount Sinai Hospital Medical Center, Illinois 60608, USA.
Gatan
M
M
Schumer
W
W
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002432:Cecum; D019446:Endotoxemia / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007116:Immunization, Passive; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010538:Peritonitis; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000201:enzymology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000906:Antibodies; D001786:Blood Glucose; D008070:Lipopolysaccharides; D008112:Liver Glycogen; D014409:Tumor Necrosis Factor-alpha; D010729:Phosphoenolpyruvate Carboxykinase (GTP)