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1Centre of Inflammation and Metabolism, Department of Infectious Diseases and Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Faculty of Health Sciences; 2Intensive Care Unit, Rigshospitalet, Copenhagen; and 3Department of Diabetes and Endocrinology M, Aarhus University Hospital and Institute of Pharmacology, University of Aarhus, Aarhus, Denmark
Submitted 3 August 2007 ; accepted in final form 30 November 2007
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-
, IL-6, and neutrophils and further stimulated gene expression of TNF-
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.
free fatty acids; lipopolysaccharide; inflammation
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