Tolerability and Anti‐Inflammatory Effects of Glucuronoxylomannan in Collagen‐Induced Arthritis

Abstract

This investigation was planned to assess the therapeutic efficacy of glucuronoxylomannan (GXM) in collagen-induced arthritis (CIA). GXM was isolated from culture filtrate of Cryptococcus neoformans var. gattii, serotype C. CIA was induced by the immunization of Dark Agouti rats with bovine type II collagen in incomplete Freund's adjuvant. GXM solution at two doses, 25 and 50 mg/kg, was administered intraperitoneally. Onset of i.p. injections of GXM to prevention and treatment groups was days 0 and 10 postimmunization, respectively. The WEHI-164 cell line was used for assaying tolerability, matrix metalloproteinase type 2 (MMP-2) activity and apoptosis. MMP-2 activity was assessed using zymography. For assessment of apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling method was used. The results of this experiment showed that the treatment of CIA with GXM at a dose of 50 mg/kg could suppress disease development both prophylactically and therapeutically. This beneficial effect of GXM was associated with a significant decrease in the anti-CII antibody response compared with untreated rats. Moreover, GXM therapy could diminish MMP-2 activity, but it had no notable effect on apoptosis. GXM also showed a high tolerability compared with certain steroidal and non-steroidal anti-inflammatory drugs. We conclude that GXM suppresses the development of disease in CIA and it could be recommended as a new immunosuppressive and anti-inflammatory agent for further investigations.

Extracellular Vesicles from Cryptococcus neoformans Modulate Macrophage Functions

“…It is noteworthy that CAP67 vesicles induced an even higher production of TNF-␣ in comparison to HEC3393 vesicles (Fig. 3), possibly because these fractions lack GXM, which causes potent depressive effects on immune function (44,45,70,73). IL-10 and TGF-␤ levels were increased following exposure to either vesicle fraction (Fig.…”

A Microbial Polysaccharide Reduces the Severity of Rheumatoid Arthritis by Influencing Th17 Differentiation and Proinflammatory Cytokines Production

“…However, high doses of GXM (500 g/ml) are not toxic to immune cells in vitro, and these doses injected in mice do not alter hematological parameters in vivo (unpublished results). Moreover, a previous study demonstrated the high tolerability of GXM compared with some steroids such as Dex and other nonsteroidal antiinflammatory drugs (43).…”

Levels of L‐Selectin (CD62L) on Human Leukocytes in Disseminated Cryptococcosis With and Without Associated HIV‐1 Infection

“…The results of a variety of in vivo and in vitro studies have suggested that cryptococcal polysaccharide triggers the shedding of L-selectin from leukocytes [5][6][7][8][9][10][11][12]. L-selectin on the surfaces of leukocytes is involved in the initial binding and rolling of leukocytes, a process that precedes extravasation into infected tissues and lymph nodes [13,15,18].…”

“…component, glucuronoxylomannan (GXM), has a key role in suppressing the inflammatory recruitment of leukocytes [5][6][7][8][9][10]. HIV-infected patients with cryptococcal meningitis have ratios of GXM in serum to GXM in CSF that inversely correlate with the numbers of leukocytes in CSF [6].…”

“…HIV-infected patients with cryptococcal meningitis have ratios of GXM in serum to GXM in CSF that inversely correlate with the numbers of leukocytes in CSF [6]. Intravascular GXM has been shown to inhibit the recruitment of neutrophils, monocytes, and lymphocytes into peripheral gelatin sponges that contain an acute inflammatory stimulus in the mouse model [7] and into the CSF of rabbits with bacterial meningitis [8]; to inhibit the progression of group B streptococcal arthritis [9]; and to suppress collagen-induced arthritis in rats [10]. Because of such findings, there is growing interest in discovering the mechanisms by which circulating capsular polysaccharide inhibits leukocyte migration from the bloodstream into infected tissues.…”