title: Glucuronoxylomannan, the major capsular polysaccharide of Cryptococcus neoformans, inhibits the progression of group B streptococcal arthritis.
abstract: Glucuronoxylomannan (GXM), the principal constituent of the Cryptococcus neoformans capsule, modulates the inflammatory response of human monocytes in vitro. Here we examine the efficacy of GXM as a novel anti-inflammatory compound for use against experimental septic arthritis. Arthritis was induced in mice by the intravenous injection of 8 x 10(6) CFU of type IV group B streptococcus (GBS). GXM was administered intravenously in different doses (50, 100, or 200 microg/mouse) 1 day before and 1 day after bacterial inoculation. GXM treatment markedly decreased the incidence and severity of articular lesions. Histological findings showed limited periarticular inflammation in the joints of GXM-treated mice, confirming the clinical observations. The amelioration of arthritis was associated with a significant reduction in the local production of interleukin-6 (IL-6), IL-1beta, macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-2 and an increase in systemic IL-10 levels. Moreover, peritoneal macrophages derived from GXM-treated mice and stimulated in vitro with heat-inactivated GBS showed a similar pattern of cytokine production. The present study provides evidence for the modulation of the inflammatory response by GXM in vivo and suggests a potential therapeutic use for this compound in pathologies involving inflammatory processes.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, Microbiology Section, University of Perugia, Via del Giochetto, 06122, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Tissi
authors.forename: Manuela
authors.initials: M
authors.lastname: Puliti
authors.forename: Francesco
authors.initials: F
authors.lastname: Bistoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Mosci
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kozel
authors.forename: Anna
authors.initials: A
authors.lastname: Vecchiarelli
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001170:Arthritis, Infectious / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D003455:Cryptococcus neoformans / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D011134:Polysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D013292:Streptococcus agalactiae / Q000187:drug effects* / Q000472:pathogenicity; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D011134:Polysaccharides; C027478:glucuronoxylomannan