UNLABELLED: 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. AIM: 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.
UNLABELLED: 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. AIM: 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.
Authors: Meir Mizrahi; Tomer Adar; Gadi Lalazar; Dean Nachman; Madi El Haj; Ami Ben Ya'acov; Yoav Lichtenstein; Yehudit Shabat; Dimitri Kanovich; Lida Zolotarov; Yaron Ilan Journal: J Clin Transl Hepatol Date: 2018-02-14