Inflammatory cytokines stimulate glucose uptake and glycolysis but reduce glucose oxidation in human dermal fibroblasts in vitro.
Interleukin-1 alpha (IL-1 alpha) produced alterations in human dermal fibroblast glucose metabolism in vitro of the type seen in severe sepsis in man. Glycolysis and glucose uptake were increased but the oxidation of glucose within the tricarboxylic acid (TCA) cycle was reduced. The combined addition of tumour necrosis factor alpha (TNF alpha) with interferon-gamma (IFN-gamma) similarly increased the dependency for cellular energy provision from an oxidative to the glycolytic state. These cytokine-induced changes in glucose metabolism were unaffected when prostaglandin production was inhibited with a cyclo-oxygenase inhibitor, but were significantly reduced by the steroid dexamethasone. Thus, the inflammatory cytokines IL-1 and TNF alpha reportedly detected in the circulation during severe sepsis may directly affect not only glucose uptake but also its subsequent metabolism within tissue fibroblasts.
Taylor
D J
DJ
University Dept. of Medicine, University Hospital of South Manchester, U.K.
Faragher
E B
EB
Evanson
J M
JM
D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002952:Citric Acid Cycle / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000494:pharmacology; D012772:Shock, Septic / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma; D005947:Glucose; D007213:Indomethacin