INSULIN-LIKE GROWTH FACTOR-I STIMULATION OF LYMPHOPOIESIS

We show that treatment of adult mice with recombinant human insulin-li ke growth factor 1 (rhIGF-1 ) induces striking modifications in lympho cyte number and function. 9-mo-old male mice received rhIGF-1 (4 mg/kg per d) or its excipient by subcutaneous infusion from osmotic minipum ps for 7 or 14 d. Mice were weighed daily and bled at sacrifice; the s pleen and thymus were harvested and single cell suspensions were made for analysis of cell phenotype and cell number. The responses of splen ocytes to mitogens (concanavalin A, lipopolysaccharide, and pokeweed m itogen), alloantigens and dinitrophenyl ovalbumin were measured. After either 7 or 14 d of treatment, rhIGF-1 had an overall whole-body anab olic effect, resulting in increased body and organ weights with promin ent increases in the weight of the spleen and thymus. Furthermore, the rhIGF-1 treated mice were normoglycemic but had reduced blood urea ni trogens, again reflecting the anabolic activity of rhIGF-1. The increa sed 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 enhance d responsiveness to dinitrophenyl ovalbumin resulting in increased imm unoglobulin production. However, despite the increases in cellularity, there was a decrease in the in vitro responses of spleen cells to mit ogens after 7 d of rhIGF-1 treatment. In contrast, treatment with rhIG F-1 for 14 d increased both the cell number and mitogenic responses of splenocytes suggesting that some time is required for the cells popul ating the peripheral organs to gain mitogenic responsiveness. It is cl ear from these data that rhIGF-1, at doses that have whole-body anabol ic activity, can expand cell number in lymphoid tissue in a normal adu lt mouse. These dual effects of rhIGF-1, of increasing lymphocyte numb er 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.