Effect of short-term intralipid infusion on the immune response during low-dose endotoxemia in humans.
Novel anti-inflammatory effects of insulin have recently been described, and insulin therapy to maintain euglycemia suppresses the plasma levels of free fatty acids (FFA) and increases the survival of critically ill patients. We aimed to explore the effect of short-term high levels of plasma FFA on the inflammatory response to a low dose of endotoxin. Fourteen healthy male volunteers underwent the following two trials in a randomized crossover design: 1) continuous infusion of 20% Intralipid [0.7 ml.kg(-1).h(-1) (1.54 g/kg)] for 11 h, and 2) infusion of isotonic saline for 11 h (control). In each trial, heparin was given to activate lipoprotein lipase, and an intravenous bolus of endotoxin (0.1 ng/kg) was given after 6 h of Intralipid/saline infusion. Blood samples and muscle and fat biopsies were obtained before the Intralipid/saline infusion and before as well as after infusion of an endotoxin bolus. Plasma levels of FFA, triglycerides, and glycerol were markedly increased during the Intralipid infusion. Endotoxin exposure induced an increase in plasma levels of TNF-alpha, IL-6, and neutrophils and further stimulated gene expression of TNF-alpha and IL-6 in both skeletal muscle and adipose tissue. The systemic inflammatory response to endotoxin was significantly pronounced during Intralipid infusion. Short-term hyperlipidemia enhances the inflammatory response to endotoxin, and skeletal muscle and adipose tissue are capable of producing essential inflammatory mediators after endotoxin stimulation.
Rigshospitalet, Section 7641, Blegdamsvej 9, Copenhagen, Denmark. krogh-madsen@inflammation-metabolism.dk
Rikke
R
Krogh-Madsen
Peter
P
Plomgaard
Thorbjorn
T
Akerstrom
Kirsten
K
Møller
Ole
O
Schmitz
Bente Klarlund
BK
Pedersen
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D001772:Blood Cell Count; D018592:Cross-Over Studies; D016207:Cytokines / Q000096:biosynthesis; D019446:Endotoxemia / Q000276:immunology* / Q000473:pathology; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007249:Inflammation / Q000473:pathology; D007262:Infusions, Intravenous; D007958:Leukocyte Count; D050356:Lipid Metabolism / Q000187:drug effects; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D009000:Monocytes; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D018950:Lipopolysaccharide Receptors; D012313:RNA; D005947:Glucose