title: A purified capsular polysaccharide markedly inhibits inflammatory response during endotoxic shock.
abstract: Capsular material of the opportunistic fungus Cryptococcus neoformans is composed mainly of a polysaccharide named glucuronoxylomannan (GXM). In this study, the effects of GXM were analyzed in an in vivo experimental system of lipopolysaccharide (LPS)-induced shock. Endotoxic shock was induced in mice by a single intraperitoneal injection of LPS from Escherichia coli. GXM treatment reduced the mortality of mice at early stages. Mice treated with LPS alone showed markedly increased plasma levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6, whereas mice that were also treated with GXM showed significantly lower plasma levels of these cytokines. This effect was related to a marked suppression of Akt and IκBα activation. Importantly, the inhibitory effect of GXM on proinflammatory cytokine secretion was reproduced by treatment with wortmannin, an inhibitor of the Akt transcription pathway. Our results indicate that GXM has a beneficial effect on endotoxic shock, resulting in a significant increase in the rate of survival by dampening the hyperinflammatory response.
authors.affiliation: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Piccioni
authors.forename: C
authors.initials: C
authors.lastname: Monari
authors.forename: S
authors.initials: S
authors.lastname: Kenno
authors.forename: E
authors.initials: E
authors.lastname: Pericolini
authors.forename: E
authors.initials: E
authors.lastname: Gabrielli
authors.forename: D
authors.initials: D
authors.lastname: Pietrella
authors.forename: S
authors.initials: S
authors.lastname: Perito
authors.forename: F
authors.initials: F
authors.lastname: Bistoni
authors.forename: T R
authors.initials: TR
authors.lastname: Kozel
authors.forename: A
authors.initials: A
authors.lastname: Vecchiarelli
mesh_terms: D000818:Animals; D003455:Cryptococcus neoformans / Q000276:immunology / Q000378:metabolism; D051550:I-kappa B Kinase / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000097:blood / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D011134:Polysaccharides / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D044967:Serum / Q000276:immunology / Q000378:metabolism; D012772:Shock, Septic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; C027478:glucuronoxylomannan; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase