Clark R, Strasser J, McCabe S, Robbins K, Jardieu P
Department of Endocrine Research, Genentech, Inc., South San Francisco, California 94080.
J Clin Invest. 1993 Aug;92(2):540-8. doi: 10.1172/JCI116621.
We show that treatment of adult mice with recombinant human insulin-like growth factor 1 (rhIGF-1) induces striking modifications in lymphocyte number and function. 9-mo-old male mice received rhIGF-1 (4 mg/kg per d) or its excipient by subcutaneous infusion from osmotic minipumps for 7 or 14 d. Mice were weighed daily and bled at sacrifice; the spleen and thymus were harvested and single cell suspensions were made for analysis of cell phenotype and cell number. The responses of splenocytes to mitogens (concanavalin A, lipopolysaccharide, and pokeweed mitogen), alloantigens and dinitrophenyl ovalbumin were measured. After either 7 or 14 d of treatment, rhIGF-1 had an overall whole-body anabolic effect, resulting in increased body and organ weights with prominent increases in the weight of the spleen and thymus. Furthermore, the rhIGF-1 treated mice were normoglycemic but had reduced blood urea nitrogens, again reflecting the anabolic activity of rhIGF-1. The increased spleen and thymus weights were associated with a large increase in the number of lymphocytes in both organs. In addition to an increase in T cells, specifically CD4+ T cells, a dramatic increase in splenic B cells was also observed. This increase was accompanied by an enhanced responsiveness to dinitrophenyl ovalbumin resulting in increased immunoglobulin production. However, despite the increases in cellularity, there was a decrease in the in vitro responses of spleen cells to mitogens after 7 d of rhIGF-1 treatment. In contrast, treatment with rhIGF-1 for 14 d increased both the cell number and mitogenic responses of splenocytes suggesting that some time is required for the cells populating the peripheral organs to gain mitogenic responsiveness. It is clear from these data that rhIGF-1, at doses that have whole-body anabolic activity, can expand cell number in lymphoid tissue in a normal adult mouse. These dual effects of rhIGF-1, of increasing lymphocyte number and activity, indicate that, in a normal adult animal, rhIGF-1 can cause major changes in lymphoid tissues that are of potential benefit to the functioning of the immune system.
我们发现，用重组人胰岛素样生长因子1（rhIGF-1）治疗成年小鼠会引起淋巴细胞数量和功能的显著改变。9月龄雄性小鼠通过渗透微型泵皮下输注rhIGF-1（4毫克/千克/天）或其赋形剂，持续7天或14天。每天称小鼠体重，处死时取血；收获脾脏和胸腺，制备单细胞悬液用于分析细胞表型和细胞数量。检测脾细胞对有丝分裂原（刀豆球蛋白A、脂多糖和商陆有丝分裂原）、同种抗原和二硝基苯基卵清蛋白的反应。治疗7天或14天后，rhIGF-1具有整体的全身合成代谢作用，导致体重和器官重量增加，脾脏和胸腺重量显著增加。此外，rhIGF-1治疗的小鼠血糖正常，但血尿素氮降低，再次反映了rhIGF-1的合成代谢活性。脾脏和胸腺重量增加与两个器官中淋巴细胞数量大幅增加有关。除了T细胞增加，特别是CD4+T细胞增加外，还观察到脾脏B细胞显著增加。这种增加伴随着对二硝基苯基卵清蛋白反应性增强，导致免疫球蛋白产生增加。然而，尽管细胞数量增加，但rhIGF-1治疗7天后，脾细胞对有丝分裂原的体外反应却降低了。相反，用rhIGF-1治疗14天增加了脾细胞的数量和有丝分裂反应，这表明外周器官中的细胞需要一些时间才能获得有丝分裂反应性。从这些数据可以清楚地看出，在具有全身合成代谢活性的剂量下，rhIGF-1可以使正常成年小鼠淋巴组织中的细胞数量增加。rhIGF-1增加淋巴细胞数量和活性的双重作用表明，在正常成年动物中，rhIGF-1可引起淋巴组织的重大变化，这可能对免疫系统的功能有益。
