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Cytokines Reduce Toxic Effects of Ethanol on Oligodendroglia

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Abstract

To characterize immunomodulatory mechanisms that affect oligodendroglia (OL) and white matter following ethanol exposure during early CNS development, we investigated the direct effects of ethanol and cytokines on glia. Mixed glial cultures from newborn rat brain were exposed to 6.5–130 mM ethanol for 1–3 days. OL were sensitive to ethanol, with death ranging from 32 to 88% with increasing time and ethanol concentrations. Little cell death occurred in astroglia or microglia. Mixtures of cytokines representative of those produced by pro-inflammatory Th1 and monocyte/macrophage (M/M) cells as well as those produced by anti-inflammatory Th2 cells were all protective. Three of the cytokines in the Th1 mixture, IL-2, TNF-α and IFN-γ, were protective individually, although no single cytokine was as effective as the mixture. The protective effects of the Th1 mixture and of IL-2 were reversed by inhibition of both MAP kinase and PI-3 kinase signaling pathways. We conclude that cytokines can act either directly on OL or indirectly through effects on astroglia or microglia to protect OL from ethanol toxicity.

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Acknowledgments

We are pleased to contribute this paper in recognition of Dr. Robert Yu for his many outstanding scientific contributions in the areas of glycosphingolipid structure and function, myelin biology, neuroimmunology, and peripheral nerve disease. We especially appreciate his enthusiastic leadership and support for neurochemistry, and his friendship with many colleagues over the years. This research was supported by the National Multiple Sclerosis Society, RG3595A7 (JAB), the Mary Parker Neuroscience Fund (RPL) and the Parker Webber Endowed Chair (RPL).

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Authors and Affiliations

  1. Department of Neurology, Wayne State University School of Medicine, 1228 Elliman Building, 421 E. Canfield Ave., Detroit, MI, 48201, USA

    Joyce A. Benjamins & Liljana Nedelkoska

  2. Department of Neurology, Wayne State University School of Medicine, 8D UHC, 4201 St. Antoine Ave., Detroit, MI, 48201, USA

    Robert P. Lisak

  3. Merrill Palmer Skillman Institute, Wayne State University, Detroit, MI, 48202, USA

    John H. Hannigan

  4. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    John H. Hannigan & Robert J. Sokol

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  1. Joyce A. Benjamins
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  2. Liljana Nedelkoska
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  3. Robert P. Lisak
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  5. Robert J. Sokol
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Correspondence to Joyce A. Benjamins.

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Special Issue: In Honor of Dr. Robert Yu.

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Benjamins, J.A., Nedelkoska, L., Lisak, R.P. et al. Cytokines Reduce Toxic Effects of Ethanol on Oligodendroglia. Neurochem Res 36, 1677–1686 (2011). https://doi.org/10.1007/s11064-011-0401-x

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