Characterization of Immunoreactive Insulin-Like Growth Factor-I from Leukocytes and Its Regulation by Growth Hormone*

Baxter, Judith B.; Blalock, J. Edwin; Weigent, Douglas A.

doi:10.1210/endo-129-4-1727

Cited by 98 publications

(31 citation statements)

References 19 publications

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“…Cells of the immune system, such as T and B lymphocytes and macrophages, express functional IGF-I receptors (17,18). Moreover, since IGF-I is produced by immune cells (19), its effects on immune responses may be secondary to autocrine or paracrine mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Stimulating effect of growth hormone on cytokine release in children

Bozzola

Benedetti²,

Amici

et al. 2003

European Journal of Endocrinology

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Objective: The aim of the present study was to investigate the effect of exogenously administered GH on serum levels of interleukin (IL)-1b, IL-2, IL-12, tumor necrosis factor (TNF)-a and interferon (IFN)-g and their relation with IGF-I levels in normal short stature children. Design and methods: 23 short prepubertal non GH-deficient children (10 females and 13 males) whose mean^S.D. chronological age was 11.95^1.85 years (from 8.80 to 14.89 years), and mean^S.D. bone age was 10.48^2.44 years, were evaluated during a somatomedin generation test (human GH 0.1 IU/kg per day for 4 days) to exclude a partial GH resistance as the cause of short stature; 34 sex-and age-matched healthy subjects were studied as controls. Circulating cytokine values were measured in basal conditions in all children, and 12 h following the 4th GH subcutaneous injection in the 23 short children only. Results: No significant differences were found between short children and controls in basal values of serum .2 ng/ml respectively). In short subjects there was a significant increase in serum IGF-I levels after the 4th GH injection (from 192.1^18.3 ng/ml, i.e. 2 1.16^0.16 standard deviation score (SDS) to 338.2^27.1 ng/ml, i.e. 0.14^0.17; P , 0.00001). No significant differences were found between short children and controls in basal concentrations of serum INF-g (19^4 and 26^5 mIU/ml respectively), IL-1a (24.950^3.613 and 20.896^2.778 pg/ml respectively), IL-2 (3.945^1.209 and 4.794^0.562 pg/ml respectively), IL-12 (1.093^0.269 and 1.976^0.596 pg/ml respectively), and TNF-a (1.794^0.559 and 2.188^0.346 pg/ml respectively). Likewise, a significant increase was found in serum INF-g (before 19^4 and after four GH injections 185^57 mIU/ml respectively; P , 0.008), IL-1b (24.950^3.613 to 43.339^5.431 pg/ml respectively; P , 0.0001), IL-2 (3.945^1.209 to 9.165^2.331 pg/ml respectively; P , 0.003), IL-12 (1.093^0.269 to 3.724^0.637 pg/ml respectively; P , 0.0007) and TNF-a (1.794^0.559 to 9.266^3.066 pg/ml respectively; P , 0.01). Conclusions: Cytokine release can be affected by short-term GH administration in normal children indicating a direct influence of GH on the immune system.

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Section: Discussionmentioning

confidence: 99%

Stimulating effect of growth hormone on cytokine release in children

Bozzola

Benedetti²,

Amici

et al. 2003

European Journal of Endocrinology

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“…4). Previously, GH has been shown to increase IGF-I secretion of splenocytes [24], thymocytes [25]and lymphocytes [26]. The T-cell mitogen PHA has been reported to increase GH secretion of PBMC in vitro [27, 28]or to have no effect [29].…”

Section: Discussionmentioning

confidence: 99%

Differential Regulation of Insulin-Like Growth Factor-(IGF) I and IGF-Binding Protein (IGFBP) Secretion by Human Peripheral Blood Mononuclear Cells

Auernhammer

Fottner²,

Engelhardt³

et al. 2002

Horm Res Paediatr

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Background: Recent studies have shown that immunocompetent cells synthesize and express growth hormone (GH), growth hormone receptors (GH-R), insulin-like growth factor I (IGF-I), IGF-I receptors (IGF-I-R) and different insulin-like growth factor binding proteins (IGFBPs). The aim of the current study was to evaluate the regulation of IGFBP and IGF-I secretion from immunocompetent cells by different mitogens. Methods/Results: We studied the in vitro secretion pattern of IGFBPs and IGF-I from human peripheral blood mononuclear cells (PBMC), derived from 10 normal adults and 8 GH-deficient patients with adult onset. In serum-free conditioned medium of unstimulated PBMC, derived from normal adults, Western ligand blotting (1D-WLB) revealed a 24-kD, a 34-kD and a 39/43-kD doublet band to be most prominent. According to their molecular weight and two-dimensional Western ligand blot analysis (2D-WLB), these bands are deglycosylated IGFBP-4, IGFBP-2 and IGFBP-3, respectively. When the cells were treated with the T-cell mitogen phytohemagglutinin (PHA) (10 µg/ml), a differential stimulation of IGFBPs was found with a 2.57 ± 0.48-fold increase of IGFBP-4 (p < 0.01), a 1.55 ± 0.13-fold increase of IGFBP-2 (p < 0.01), and a 1.35 ± 0.19-fold increase of IGFBP-3 (n.s.). In contrast, treatment with the B-cell mitogen pokeweed mitogen (PWM) (10 µg/ml) caused only a modest 1.40 ± 0.07-fold increase of IGFBP-4 (p < 0.01). Treatment with rhGH (100 ng/ml) or rhIGF-I (200 ng/ml) caused no significant induction of any specific band, respectively. In contrast to the secretion pattern of IGFBPs, IGF-I secretion of the PBMC was not stimulated by either PHA or PWM, but showed a significant increase after GH incubation (p < 0.01). A similar differentiated secretion pattern of IGFBPs and IGF-I was also observed in the conditioned medium of PBMC, derived from GH-deficient patients. Conclusion: In summary, at least three different IGFBPs are secreted by human PBMC. Secretion of IGFBPs by PBMC is differentially regulated by different lymphocyte mitogens. Secretion of IGFBPs by PBMC is independent of GH or IGF-I, whereas the secretion of IGF-I is stimulated by GH. PBMC derived from normal adults and GH-deficient patients show similar patterns of IGF-I and IGFBPs secretion, thus indicating that the paracrine/autocrine IGF-I–IGFBPs interactions of the PBMC are not altered by pituitary GH deficiency.

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“…in some aspects of immune function (Binz et al 1990;Baxter et al 1991;Beschorner et al 1991;Landreth et al 1992;Timsit et al 1992).…”

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confidence: 99%

IGF-I is required for normal embryonic growth in mice.

Powell-Braxton¹,

Hollingshead²,

Warburton³

et al. 1993

Genes & Development

722

465

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IGF-I is a pleiotropic hormone reported to affect linear growth, glucose metabolism, organ homeostasis, and the immune and neurologic systems. In contrast to IGF-II, IGF-I is expressed at low levels embryonically and has been thought to be more important for postnatal growth and development. To investigate the role of IGF-I in normal development we generated mice with an inactive IGF-I gene by homologous recombination in ES cells. Heterozygous mice are healthy and fertile, but they are 10-20% smaller than wild-type littermates and have lower than normal levels of IGF-I. The size reduction is attributable to a decrease in organs and muscle and bone mass. However, all tissues appear histologically normal. At birth homozygous mutant mice (IGF-I -/-) are <60% body weight of wild type. Greater than 95% of IGF-I -/-pups die perinatally. Histopathology is characterized by underdevelopment of muscle tissue. Lungs of late embryonic and neonates also appeared less organized with ill-defined alveolae. IGF-I appears to be essential for correct embryonic development in mice.

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Characterization of Immunoreactive Insulin-Like Growth Factor-I from Leukocytes and Its Regulation by Growth Hormone*

Cited by 98 publications

References 19 publications

Stimulating effect of growth hormone on cytokine release in children

Stimulating effect of growth hormone on cytokine release in children

Differential Regulation of Insulin-Like Growth Factor-(IGF) I and IGF-Binding Protein (IGFBP) Secretion by Human Peripheral Blood Mononuclear Cells

IGF-I is required for normal embryonic growth in mice.

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