二：重组人胰岛素样生长因子-1对营养不良酒精性大鼠免疫恢复的影响。

II: the effects of recombinant human insulin-like growth factor-1 on immunological recovery in the malnourished alcoholic rat.

作者信息

Mendenhall C L, Roselle G A, Grossman C J, Gartside P

机构信息

Department of Veterans Affairs Medical Center, and Department of Medicine, University of Cincinnati Medical Center, Ohio 45220, USA.

出版信息

Alcohol Clin Exp Res. 1997 Dec;21(9):1682-9. doi: 10.1111/j.1530-0277.1997.tb04507.x.

DOI:10.1111/j.1530-0277.1997.tb04507.x

PMID:9438530

Abstract

BACKGROUND/AIMS: Immunological abnormalities are frequently observed in alcoholics with severe liver disease and are typically in association with immune abnormalities. Concomitantly, serum levels of insulin-like growth factor-1 (IGF-1) are frequently very low in these patients. Because IGF-1 is known to modulate both nutrition and immune status, the present study was undertaken to evaluate an in vivo rat model of alcoholism and malnutrition, the possibility of a therapeutic application for IGF-1.

METHODS

Controlled injury was induced by 14 days of calorie restriction and alcohol feeding that resulted in a 9% loss of body mass. Changes were compared with normal unrestricted control rats that gained 28% above their pretreatment body mass during the same period. Immunological impairment was assessed using thymus and spleen mass, cellularity and spleen T-lymphocyte function. Recovery was evaluated after 28 days of treatment using various combinations of: (1) high calorie intake, (2) cessation from alcohol feeding, and (3) IGF-1.

RESULTS

The thymus was most severely affected, losing 52.3% of its mass and 55.7% of its cellularity. The spleen was diminished, losing 31.2% of its mass and 41.9% of its cellularity. All of the spleen T-lymphocyte subsets were diminished, with CD5 affected the least (37.1 %) and CD8 affected the most severely (51.7%). During recovery, only the group treated with high calorie intake, no alcohol intake, and IGF-1 (group 8) had complete restoration of all immunological parameters, including a recovery of T-lymphocyte function. Continuous consumption of alcohol, even in the presence of high calories and IGF-1, produced an incomplete recovery.

CONCLUSIONS

Cessation of alcohol coupled with high calorie nutrition and IGF-1 treatment produced an accelerated improvement in host immunity. These animal studies suggest that IGF-1 is efficacious for this condition and supports the need for additional clinical studies.

摘要

背景/目的：免疫异常在患有严重肝病的酗酒者中经常被观察到，并且通常与免疫异常相关。与此同时，这些患者的血清胰岛素样生长因子-1（IGF-1）水平通常非常低。由于已知IGF-1可调节营养和免疫状态，因此本研究旨在评估酒精中毒和营养不良的体内大鼠模型以及IGF-1的治疗应用可能性。

方法

通过14天的热量限制和酒精喂养诱导可控损伤，导致体重减轻9%。将变化与同期体重比预处理体重增加28%的正常非限制对照大鼠进行比较。使用胸腺和脾脏质量、细胞数量和脾脏T淋巴细胞功能评估免疫损伤。在治疗28天后，使用以下各种组合评估恢复情况：（1）高热量摄入，（2）停止酒精喂养，（3）IGF-1。

结果

胸腺受影响最严重，质量损失52.3%，细胞数量损失55.7%。脾脏缩小，质量损失31.2%，细胞数量损失41.9%。所有脾脏T淋巴细胞亚群均减少，其中CD5受影响最小（37.1%），CD8受影响最严重（51.7%）。在恢复过程中，只有接受高热量摄入、不摄入酒精和IGF-1治疗的组（第8组）所有免疫参数完全恢复，包括T淋巴细胞功能的恢复。即使存在高热量和IGF-1，持续饮酒也会导致恢复不完全。