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Lack of IL-6 increases blood–brain barrier permeability in fungal meningitis

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Abstract

The pathogenesis of increased blood–brain barrier permeability during Cryptococcus meningitis is still largely unknown. Interleukin (IL-6) is a multifunctional cytokine, and numerous studies have shown that IL‐6 influences the integrity of the blood–brain barrier. In this study we investigated the role of IL-6 in Cryptococcus meningitis. First, wild-type or IL-6−/− mice were injected with Cryptococcus neoformans (C. neoformans) and the survival time in both groups was recorded. Second, the number of fungi was measured in the brains of IL-6−/− wild-type mice. Finally, the blood–brain barrier permeability index was detected in infected IL-6−/− mice treated with recombinant human IL-6. The blood–brain barrier permeability index was measured in infected wild-type mice treated with anti-IL-6 antibodies as well. The survival of IL-6−/− mice injected with C. neoformans was significantly lower than that of identically challenged wild-type mice. The infected IL-6−/− mice had significantly larger brain fungal burdens than wild-type mice. Furthermore, increased blood–brain barrier index was found in infected IL-6−/− mice when compared with that in infected control mice. Similar results were obtained when mice challenged with C. neoformans were treated systemically with neutralizing anti-IL-6 antibodies, resulting in an elevation of vascular permeability. Our data revealed that IL-6 reduced the blood–brain barrier permeability during Cryptococcus meningitis, and it might provide an explanation for the significantly lower survival of infected IL-6−/− mice.

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Correspondence to Xiang Li.

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Corresponding editor: Satyajit Rath

[Li X, Liu G, Ma J, Zhou L, Zhang Q and Gao L 2015 Lack of IL-6 increases blood–brain barrier permeability in fungal meningitis. J. Biosci. 40 1–6] DOI 10.1007/s12038-014-9496-y

Supplementary materials pertaining to this article are available on the Journal of Biosciences Website at http://www.ias.ac.in/jbiosci/mar2015/supp/Li.pdf

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Li, X., Liu, G., Ma, J. et al. Lack of IL-6 increases blood–brain barrier permeability in fungal meningitis. J Biosci 40, 7–12 (2015). https://doi.org/10.1007/s12038-014-9496-y

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