PMID- 25740137 OWN - NLM STAT- MEDLINE DCOM- 20151229 LR - 20190918 IS - 0973-7138 (Electronic) IS - 0250-5991 (Linking) VI - 40 IP - 1 DP - 2015 Mar TI - Lack of IL-6 increases blood-brain barrier permeability in fungal meningitis. PG - 7-12 AB - 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. FAU - Li, Xiang AU - Li X AD - Department of Pharmacy, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China, lxbj@hotmail.com. FAU - Liu, Guiyang AU - Liu G FAU - Ma, Jianli AU - Ma J FAU - Zhou, Liang AU - Zhou L FAU - Zhang, Qingzhe AU - Zhang Q FAU - Gao, Lei AU - Gao L LA - eng PT - Journal Article PL - India TA - J Biosci JT - Journal of biosciences JID - 8100809 RN - 0 (Antibodies) RN - 0 (Interleukin-6) RN - 0 (Recombinant Proteins) SB - IM MH - Animals MH - Antibodies/immunology/pharmacology MH - Blood-Brain Barrier/*pathology MH - Brain/blood supply/microbiology/*physiopathology MH - Cryptococcosis/microbiology/mortality/*pathology MH - Cryptococcus neoformans/growth & development/immunology MH - Humans MH - Interleukin-6/genetics/immunology/*pharmacology MH - Male MH - Meningitis, Fungal/microbiology/mortality/*pathology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Recombinant Proteins/genetics/pharmacology EDAT- 2015/03/06 06:00 MHDA- 2015/12/30 06:00 CRDT- 2015/03/06 06:00 PHST- 2015/03/06 06:00 [entrez] PHST- 2015/03/06 06:00 [pubmed] PHST- 2015/12/30 06:00 [medline] AID - 10.1007/s12038-014-9496-y [doi] PST - ppublish SO - J Biosci. 2015 Mar;40(1):7-12. doi: 10.1007/s12038-014-9496-y.