Neuroprotective role of IL-4 against activated microglia.
Microglia have been proposed to play a pathogenetic role in immunologically mediated neurodegenerative diseases. In our study, using microglial/neuronal cell cocultures primed with IFN-gamma, we found that both LPS and TNF-alpha triggered neuronal cell injury (impairment of gamma-aminobutyric acid uptake and neuronal loss) via a nitric oxide mechanism. Pretreatment of cell cocultures with IL-4, an immunosuppressive cytokine, prevented, in a dose-dependent manner, neuronal cell injury induced by activated microglia. The mechanism by which IL-4 exerts its neuroprotective effect was found to involve the inhibition of IFN-gamma priming of microglia with a subsequent decrease in the production of TNF-alpha and nitric oxide.
Chao
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Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404.
Molitor
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Hu
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D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009474:Neurons / Q000166:cytology / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D007770:L-Lactate Dehydrogenase