Insulin-like growth factor-1 stimulation of lymphopoiesis.

Abstract

IntroductionWe 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. (J.

Insulin-like growth factor-binding protein-4 inhibits growth of the thymus in transgenic mice

“…Systemic administration of IGF-I significantly increased the size and cellularity of both primary and secondary lymphoid organs in rodents (Binz et al 1990, Beschorner et al 1991, Murphy et al 1992, Clark et al 1993. Furthermore, IGF-I administration enhanced immune response and altered lymphocyte survival and regeneration in thymus and spleen of dexamethasone-treated rats (Hinton et al 1995(Hinton et al , 1998.…”

“…Administration of IGF-II also stimulates growth of the thymus and spleen, but to a lesser extent than IGF-I (Buul-Offers et al 1994, Conlon et al 1995. Overexpression of IGF-I in mice stimulates T-and B-cell development and antigen-specific IgG synthesis (Clark et al 1993, Robbins et al 1994. Overexpression of IGF-II in transgenic mice stimulated the development of phenotypically normal T-cells but not mature B-cells (Kooijman et al 1995(Kooijman et al , 1997.…”

Aberrant Expression of the Insulin-Like Growth Factor-1 Receptor by T Cells from Patients with Graves’ Disease May Carry Functional Consequences for Disease Pathogenesis

“…Peripheral blood T and B cells and monocytes from control human donors express low levels of IGF-1R in vivo (8,9). Administration of IGF-1 increases the circulating pool of CD4 ϩ T cells and splenic B cells in mice (10,11), suggesting a role for this growth factor in myelopoietic cell expansion (12). It promotes T cell proliferation during early activation (13) and inhibits apoptosis of both immature and mature T cells through at least three distinct mechanisms (14,15).…”

Impact of the Somatotrope Growth Hormone (GH)/Insulin-Like Growth Factor 1 (IGF-1) Axis Upon Thymus Function: Pharmacological Implications in Regeneration of Immune Functions

“…These data may also suggest that IGF-1 is produced by a variety of thymic cells in a paracrine/autocrine fashion independently of GH regulation. It has also been shown that administration of rhIGF-1 in mice for one to two weeks results in an increase of thymic mass by doubling T-lymphocyte population [79]. This is further evidence showing that treatment with rhIGF-1 increases thymocyte number.…”

“…The exact mechanism is not yet known, but it has been shown that GH enhances T-cell proliferation in rodents. The implantation in aged rats of pituitary GH3 cells secreting GH increases the size of their thymus and increases thymocyte numbers [79]. In GH-and prolactin-deficient dwarf DW/J mice, GH administration increases thymic cell number and T-cell proliferation [93].…”