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Differential effects of pro- and anti-inflammatory cytokines alone or in combinations on the metabolic profile of astrocytes.

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We have previously reported that the pro-inflammatory cytokines tumor necrosis factor-a (TNFa) and interleukin-1ß (IL-1ß) induce profound modifications of the metabolic profile of astrocytes. The present study was undertaken to further characterize the effects of cytokines in astrocytes and to determine whether similar effects could also be observed in neurons. To do so, selected pro-inflammatory (IL-6 and interferon-?, in addition to the above-mentioned TNFa and IL-1ß) and anti-inflammatory cytokines (IL-4, IL-10, transforming growth factor-ß1 and interferon-ß) were applied to primary neuronal and astrocytic cultures, and key metabolic parameters were assessed. As a general pattern, we observed that pro-inflammatory cytokines increased glucose utilization in astrocytes while the anti-inflammatory cytokines IL-4 and IL-10 decreased astrocytic glucose utilization. In contrast, no significant change could be observed in neurons. When pairs of pro-inflammatory cytokines were co-applied in astrocytes, several additive or synergistic modifications could be observed. In contrast, IL-10 partially attenuated the effects of pro-inflammatory cytokines. Finally, the modifications of the astrocytic metabolism induced by TNFa + IL-1ß and interferon-? modulated neuronal susceptibility to an excitotoxic insult in neuron-astrocyte co-cultures. Together, these results suggest that pro- and anti-inflammatory cytokines differentially affect the metabolic profile of astrocytes, and that these changes have functional consequences for surrounding neurons.

Keywords: anti inflammatory cytokines, inflammatory cytokines, anti inflammatory, glucose utilization, metabolic profile, cytokines, inflammatory, astrocytes, observed, interferon, astrocytic, neurons, metabolic, effects, modifications

Authored by Bélanger M, Allaman I, Magistretti PJ. Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne (EPFL), Switzerland.

Published in J Neurochem. 2011 Feb;116(4):564-76. doi: 10.1111/j.1471-4159.2010.07135.x. Epub 2011 Jan 19. The full report is available online. link   A subscription to the periodical may be required.

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