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Lack of IL-6 increases bloodbrain barrier permeability in fungal meningitis
XIANG LI*, GUIYANG LIU, JIANLI MA, LIANG ZHOU, QINGZHE ZHANG and LEI GAO
Department of Pharmacy, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China
*Corresponding author (Fax, +861066867082; Email, [email protected])
The pathogenesis of increased bloodbrain barrier permeability during Cryptococcus meningitis is still largely unknown. Interleukin (IL-6) is a multifunctional cytokine, and numerous studies have shown that IL6 influences the integrity of the bloodbrain 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 bloodbrain barrier permeability index was detected in infected IL-6/ mice treated with recombinant human IL-6. The bloodbrain 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 bloodbrain 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 bloodbrain barrier permeability during Cryptococcus meningitis, and it might provide an explanation for the significantly lower survival of infected IL-6/ mice.
[Li X, Liu G, Ma J, Zhou L, Zhang Q and Gao L 2015 Lack of IL-6 increases bloodbrain barrier permeability in fungal meningitis. J. Biosci. 40 712] DOI 10.1007/s12038-014-9496-y
1. Introduction
C. neoformans is a ubiquitous encapsulated fungus that causes the third most common opportunistic infection of the CNS in patients with AIDS (Mwaba et al. 2001; Bicanic et al. 2009; Esposito et al. 2009). C. neoformans disseminates to the central nervous system in the immunosuppressed patient and occasion-ally in the normal host, and leads to a potentially life-threatening meningoencephalitis. Studies conducted largely in the United States suggest that between 6% and 10% of patients with AIDS develop Cryptococcus meningitis (Powderly...