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Beta glycolipids as immuno-modulators

一种糖脂、免疫相关的技术，应用在抗炎剂、抗病毒剂、抗真菌剂等方向

Inactive Publication Date: 2009-03-11
ENZO THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0021] To the best of the inventors' knowledge, no previously used method of immune modulation involved exposing components of the immune system to mammalian naturally occurring β-glycolipids, particularly mixtures of β-glycolipids

Method used

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  • Beta glycolipids as immuno-modulators

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0221] Use of beta-glycolipids for the treatment of immune-mediated colitis

[0222] To determine the effect of administration of β-glycolipids such as β-glucosylceramide (GluC), β-lactosylceramide (LacC) and β-galactosylceramide (GalC) and ceramides on experimental colitis Clinical and immunological effects in the murine model, nine groups of C57B1 mice each consisting of 10 mice were studied. As outlined in Table 1, colitis was induced by intracolonic placement of trinitrobenzenesulfonic acid (TNBS) on days 1 and 5 in groups A-E. Group A mice were fed with conventional diet. Groups B-E mice were orally administered (PO) 15 μg of GluC, LacC, GalC and ceramide each day. Group F-I mice were not treated with TNBS, but were orally administered (PO) 15 μg of GluC, LacC, GalC and ceramide every day, and were used as a control group.

[0223] The visual and microscopic colitis scores of the mice were tracked and recorded. The immunomodulatory effect of GC was determined by FACS ...

Embodiment 2

[0229] Synergistic effect of a mixture of β-glycolipids in the treatment of immune-mediated colitis

[0230] To determine the possible immunomodulatory effects of different β-glycolipids, the effect of a mixture of β-glucocerebroside (GC) and β-lactosylceramide (LC) was tested using a murine model of colitis.

[0231] As outlined in Table 2, 5 groups of mice, each consisting of 10 mice, were studied. Colitis was induced by intracolonic placement of trinitrobenzenesulfonic acid (TNBS) on days 1 and 5 in groups A, B and D. Group A mice were fed with conventional diet. Group B mice received daily oral (PO) 15 μg mixture of β-GluC (GC) and β-LacC (LC), group D received β-LacC only. Groups C and E mice were not treated with TNBS but received 15 μg daily oral (PO) of a mixture of β-GluC and β-LacC or β-LacC alone, respectively, and served as a control group.

[0232] Mice were followed for visual and microscopic colitis scores, as well as for survival and functional status and bo...

Embodiment 3

[0239] Effect of a mixture of β-glycolipids in the treatment of immune-mediated colitis

[0240] To further investigate the possible use of β-glycolipids as a drug for colitis, the inventors next determined the effect of the combination of GC and LC on intrahepatic NKT regulatory lymphocytes and lymphocyte capture.

[0241]4 groups of mice were studied. Immune-mediated colitis was induced in all groups by intracolonic placement of trinitrobenzenesulfonic acid (TNBS). Groups B-D were treated by daily administration of glucosylceramide (GC), lactosylceramide (LC) and a combination of GC and LC (1:1 ratio), respectively. Mice in control group A received vehicle only. Mice were evaluated for visual and microscopic colitis scores. The immunomodulatory effects of β-glycolipids were determined by FACS analysis of intrahepatic and intrasplenic lymphocytes for NKT, CD4 and CD8 markers and by measuring serum cytokine levels.

[0242] As shown in Table 4, administration of β-glycolip...

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Abstract

The present invention relates to a process for the modulation of the Th1 / Th2 cell balance toward anti-inflammatory cytokine producing cells, in a subject suffering from an immune related disorder. The process of the invention comprises the step of increasing the intracellular, extra-cellular or serum level of a naturally occurring beta-glycolipid in a subject in need thereof. The invention further relates to methods for the treatment of a subject suffering from an immune-related disease. Therapeutic compositions and method for the preparation of these compositions are also provided.

Description

Field of the invention [0001] The present invention relates to the use of beta-glycolipids as immunomodulators. More particularly, the present invention relates to β-glycolipids, preferably β-lactosylceramide, β-glucosylceramide, β-galactosylceramide, ceramide, most preferably β-lactosylceramide and any of them Use of a mixture or combination for the treatment of an immune-related disorder. Background of the invention [0002] Immunotherapy involves exposing components of the immune system to different components (cytokines, disease-associated antigens, and natural metabolites) to combat disease processes in which dysregulated immune responses are thought to play an important role. Immune dysregulation is thought to play a major role in the pathogenesis or course of many disease processes, including various neoplastic, inflammatory, infectious and genetic entities. [0003] These conditions, a few of which are described below in this specification, can be understood as an ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/70A61P37/00
CPCA61K31/739A61K31/70A61P1/04A61P1/16A61P11/06A61P17/00A61P19/02A61P25/00A61P29/00A61P3/00A61P3/04A61P31/04A61P31/10A61P31/12A61P33/00A61P35/00A61P35/02A61P3/06A61P37/00A61P37/02A61P37/06A61P43/00A61P9/10A61P3/10
Inventor Y·依兰
Owner ENZO THERAPEUTICS
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