Effect of recombinant cytokines on glycolysis and fructose 2,6-bisphosphate in rheumatoid synovial cells in vitro.
Recombinant-derived human interleukin 1 (IL1) alpha and beta and interferon gamma (IFN-gamma) each produced similar increases in rheumatoid synovial cell (RSC) glycolysis, as judged by increased values for glucose uptake, lactate production and cellular fructose 2,6-bisphosphate [Fru(2,6)P2]. Measurement of Fru(2,6)P2 proved to be the most sensitive parameter for an assessment of glycolysis: IL1 alpha, IL1 beta and IFN-gamma all produced a 3-6-fold increase in this metabolite whereas tumour necrosis factor (TNF alpha) was far less effective. Prostaglandin E production was stimulated predominantly by IL1 alpha and IL1 beta rather than by IFN-gamma or TNF alpha. When combinations of cytokines were examined the addition of IFN-gamma with either IL1 alpha, IL1 beta or murine IL1 produced a synergistic increase in cellular Fru(2,6)P2. The three forms of IL1 increased Fru(2,6)P2 via the same pathway, whereas IFN-gamma acted via a different mechanism. The increase in Fru(2,6)P2 in subcultured RSC produced by addition of medium from a primary culture exceeded the maximal effects of any of the single cytokines studied, suggesting the presence of a mixture of cytokines in the primary RSC culture medium.
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured; D005635:Fructosediphosphates / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D006598:Hexosediphosphates / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism*
D005635:Fructosediphosphates; D006598:Hexosediphosphates; D007375:Interleukin-1; D011458:Prostaglandins E; D011994:Recombinant Proteins; C027652:fructose 2,6-diphosphate; D007371:Interferon-gamma