Administration of beta-glycolipids overcomes an unfavorable nutritional dependent host milieu: a role for a soy-free diet and natural ligands in intrahepatic CD8+ lymphocyte trapping and NKT cell redistribution.
Soy-based diets are a major source of sphingolipids and play a complicated role in various aspects of the immune system. Administration of beta-glycolipids, including beta-glucosylceramide (GC), beta-lactosylceramide (LC) and a 1:1 combination of GC and LC (IGL) were shown to exert immune-modulatory effects.


OBJECTIVE
To examine the effects of a soy-free diet, and several beta-glycolipids on concanavalin A (ConA)-induced hepatitis in the presence of an altered host glycolipid milieu.


METHODS
ConA hepatitis was induced in C57BL/6 mice that were fed a soy-free diet (glycolipid content 200 micromol/kg). Two hours prior to administration of ConA, animals were injected IP with GC, LC, IGL or PBS. Animals were sacrificed 6 h after ConA administration.


RESULTS
Both a soy-free diet and administration of beta-glycolipids were associated with significant alterations in the distribution of NKT cells. Specifically, there was a decrease in intrahepatic and an increase in intrasplenic NKT lymphocytes. beta-glycolipids prevented the ConA-induced intrahepatic CD8 lymphocyte trapping, not seen in mice with only a soy-free diet. Both a soy-free diet and beta-glycolipids alleviated ConA-induced hepatitis by inhibiting IL10 secretion and increasing IL12 serum levels. The effect of IGL was clinically and immunological superior to that of either glycolipid alone.


CONCLUSIONS
Both a soy-free diet and beta-glycolipids can overcome the unfavorable host milieu in the setting of ConA hepatitis. The host glycolipid milieu profoundly influenced the immune and clinical effects of various insults, and suggests that alteration of the glycolipid background of the host can serve as a novel therapeutic tool.
Livovsky
Dan M
DM
Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Lalazar
Gadi
G
Ben Ya'acov
Ami
A
Pappo
Orit
O
Preston
Sarah
S
Zolotaryova
Lidya
L
Ilan
Yaron
Y
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002469:Cell Separation; D003208:Concanavalin A; D016207:Cytokines / Q000096:biosynthesis; D004032:Diet; D005434:Flow Cytometry; D006017:Glycolipids / Q000627:therapeutic use*; D019693:Hepatitis, Autoimmune / Q000178:diet therapy / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008024:Ligands; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009747:Nutritional Physiological Phenomena / Q000187:drug effects*; D013025:Glycine max; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects
D016207:Cytokines; D006017:Glycolipids; D008024:Ligands; D003208:Concanavalin A