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Glucuronoxylomannan, the Major Capsular Polysaccharide of Cryptococcus neoformans, Inhibits the Progression of Group B Streptococcal Arthritis

Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy,¹ Department of Microbiology and Immunology, University of Nevada, Reno, Nevada²

Received 7 June 2004/ Returned for modification 5 July 2004/ Accepted 21 July 2004

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 10⁶ CFU of type IV group B streptococcus (GBS). GXM was administered intravenously in different doses (50, 100, or 200 µg/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-1ß, macrophage inflammatory protein 1 (MIP-1), 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.

Editor: J. T. Barbieri

This article has been cited by other articles:

• McFadden, D. C., De Jesus, M., Casadevall, A. (2006). The Physical Properties of the Capsular Polysaccharides from Cryptococcus neoformans Suggest Features for Capsule Construction. J. Biol. Chem. 281: 1868-1875 [Abstract] [Full Text]