Lack of IL-6 increases blood-brain barrier permeability in fungal meningitis.
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.
Department of Pharmacy, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China, lxbj@hotmail.com.
Xiang
X
Li
Guiyang
G
Liu
Jianli
J
Ma
Liang
L
Zhou
Qingzhe
Q
Zhang
Lei
L
Gao
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000473:pathology*; D001921:Brain / Q000098:blood supply / Q000382:microbiology / Q000503:physiopathology*; D003453:Cryptococcosis / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D003455:Cryptococcus neoformans / Q000254:growth & development / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D016921:Meningitis, Fungal / Q000382:microbiology / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology
D000906:Antibodies; D015850:Interleukin-6; D011994:Recombinant Proteins