Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Clin Exp Immunol. 2012 Feb;167(2):252-60. doi: 10.1111/j.1365-2249.2011.04511.x.
Insulin resistance and metabolic syndrome are chronic inflammatory conditions that lead to hepatic injury and non-alcoholic steatohepatitis (NASH). Bovine colostrum has therapeutic effects in a variety of chronic infections. However its effectiveness in NASH was never studied. Natural killer T (NKT) cells have been shown to be associated with some of the pathological and metabolic abnormalities accompanying NASH in leptin-deficient (ob/ob) mice. In the present study, we used hyperimmune bovine colostrum to treat hepatic injury and insulin resistance and we also assessed the effects on NKT cells. We used ob/ob mice that were fed for 6 weeks with either 0·1 mg bovine colostrum prepared from non-immunized cows, 0·1 mg hyperimmune colostrum raised against a bacterial lipopolysaccharide (LPS) extract or 0·001, 0·1 or 1 mg of immunoglobulin (Ig)G purified from hyperimmune colostrum (IgG-LPS). NKT cells were phenotyped by flow cytometry, and hepatic injury and insulin resistance were assessed by measuring fasting glucose levels, glucose tolerance tests and liver enzymes. Fat accumulation was measured in the liver and plasma. Oral administration of hyperimmune colostrums decreased alanine aminotransferase (ALT) serum levels and serum triglycerides compared to controls. Glucose intolerance was also improved by the hyperimmune colostrum preparations. These results were accompanied by a decrease in serum tumour necrosis factor (TNF)-α levels following oral treatment with 0·1 or 1 mg of IgG-LPS. The beneficial effects of hyperimmune colostrums were associated with an increase in the number of splenic NKT cells. These data suggest that oral administration of hyperimmune colostrum preparations can alleviate chronic inflammation, liver injury and insulin resistance associated with NASH.
胰岛素抵抗和代谢综合征是慢性炎症性疾病,可导致肝损伤和非酒精性脂肪性肝炎(NASH)。牛初乳在多种慢性感染中具有治疗作用。然而,其在 NASH 中的有效性从未被研究过。自然杀伤 T(NKT)细胞已被证明与瘦素缺乏(ob/ob)小鼠中伴随 NASH 的一些病理和代谢异常有关。在本研究中,我们使用高免疫牛初乳治疗肝损伤和胰岛素抵抗,并评估其对 NKT 细胞的影响。我们使用 ob/ob 小鼠,这些小鼠在 6 周内喂食 0.1mg 来自非免疫奶牛的牛初乳、0.1mg 针对细菌脂多糖(LPS)提取物的高免疫牛初乳或 0.001、0.1 或 1mg 从高免疫牛初乳中纯化的免疫球蛋白(IgG)(IgG-LPS)。通过流式细胞术对 NKT 细胞进行表型鉴定,并通过测量空腹血糖水平、葡萄糖耐量试验和肝酶来评估肝损伤和胰岛素抵抗。通过测量肝脏和血浆中的脂肪积累来评估脂肪堆积。与对照组相比,高免疫牛初乳的口服给药降低了丙氨酸氨基转移酶(ALT)血清水平和血清甘油三酯。高免疫牛初乳制剂也改善了葡萄糖耐量。这些结果伴随着口服 0.1 或 1mg IgG-LPS 后血清肿瘤坏死因子(TNF)-α水平的降低。高免疫牛初乳的有益作用与脾 NKT 细胞数量的增加有关。这些数据表明,口服高免疫牛初乳制剂可以减轻与 NASH 相关的慢性炎症、肝损伤和胰岛素抵抗。