Serum cytokine levels in GH-deficient children during substitutive GH therapy

Pagani, Sara; Meazza, Cristina; Travaglino, Paola; Benedetti, Fabrizio; Tinelli, Carmine; Bozzola, Mauro

doi:10.1530/eje.1.01827

Cited by 28 publications

(31 citation statements)

References 20 publications

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“…Taken together, GH/IGF1 appeared to stimulate the initial phase of the innate immune response as evaluated by levels of proinflammatory cytokines, whereas the influence on levels of APPs was inconsistent. The increase in serum TNFa and IL6 induced by GH treatment is in accordance with a short-term study on children with GH deficiency where increased levels of TNFa and IL6 were observed 6 h after a single s.c. GH injection (12). A direct stimulating effect of GH is further supported by in vitro studies where both GH and IGF1 administrations seem to increase TNFa and IL6 secretion from activated lymphocytes (13,33).…”

Section: Discussionmentioning

confidence: 83%

“…In addition, more recent observations have demonstrated that the relationship may be bidirectional, with GH/IGF1 activity influencing inflammatory processes (3,10,11). However, the association seems complicated as data obtained from in vivo and in vitro studies have been supporting pro-inflammatory (3,12,13) as well as anti-inflammatory effects of GH and IGF1 (3,13,14,15).…”

Section: Introductionmentioning

confidence: 99%

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GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

Andreassen

Frystyk

Faber

et al. 2012

European Journal of Endocrinology

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Introduction: The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro-and anti-inflammatory effects have been demonstrated. Methods/design: Twelve healthy volunteers (mean age 36, range 27-49 years) were treated in random order with increasing doses of GH for 3 weeks (first week 0.01 mg/kg per day, second week 0.02 mg/kg per day, and third week 0.03 mg/kg per day) or a GH receptor antagonist (pegvisomant; first week 10 mg/day and last two weeks 15 mg/day), separated by 8 weeks of washout. Circulating levels of the pro-inflammatory cytokines tumor necrosis factor a (TNFa (TNFA)), interleukin 6 (IL6), and IL1b (IL1B) and the acute phase proteins (APPs) C-reactive protein (CRP), haptoglobin, orosomucoid, YKL40 (CHI3L1), and fibrinogen were measured. Conclusions: GH/IGF1 action appears to modulate the initial stage of the inflammatory response as well as downstream processes elucidated by levels of APPs. The data suggest a complicated relationship not allowing any simple conclusions as to whether GH/IGF1 actions have mainly pro-or antiinflammatory effects in vivo.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

Andreassen

Frystyk

Faber

et al. 2012

European Journal of Endocrinology

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“…Kappel et al induced a significant increase in neutrocyte count two hours after a bolus infusion of recombinant GH but failed to show an increase in cytokine production indicating GH may only have minor acute effects on the immune system [22]. Numerous in vitro and in vivo studies have suggested GH modulates cytokine secretion [3] [5] [6] [11] [23]. All of these studies used pharmacologic doses of GH that would have exceeded the endogenously produced serum concentrations seen in most of our subjects.…”

Section: Discussionmentioning

confidence: 99%

“…These findings suggest a role for GH in priming macrophages for TNF α synthesis [3]. Similarly, studies conducted in both normal statured and GH deficient children have illustrated significant increases in cytokine release, specifically TNF α, after short term GH administration [5] [6].…”

Section: Introductionmentioning

confidence: 90%

Relationship between Growth Hormone and Cytokines in Short Children Undergoing Growth Hormone Stimulation Testing

Tafuri¹,

Dixon²,

Markarian³

et al. 2015

IJCM

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Background: The relationship between growth hormone (GH) and cytokines remains unclear. Several studies have suggested that GH increases tumor necrosis factor (TNF)-α production in both children and adults. However, a number of studies have demonstrated a negative correlation between GH and TNF α. The aim of this study is to explore the relationship between endogenous GH secretion and certain pro and anti-inflammatory cytokines in short children undergoing GH stimulation testing for evaluation for GH deficiency. Methods: Plasma growth hormone, TNF α, CRP, IL-6, IL1-β, IL-4 and IL-10 levels are obtained at baseline and every 30 minutes for 150 minutes following two provocative agents (clonidine, and either arginine or glucagon). Results: Among the 23 children, 7 are found to be GH deficient. No significant differences in baseline TNF α levels are found between GH deficient and GH sufficient children. No correlation is identified between TNF α levels and GH levels during stimulation testing. Furthermore, no relationship is found between GH and pro-inflammatory cytokines or GH and anti-inflammatory cytokines. Conclusion: Our results do not demonstrate an acute relationship between endogenous GH secretion and the cytokines examined.

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“…It is well documented that proinflammatory cytokines increase muscle protein degradation, reduce muscle protein synthesis and divert nutrients to the synthesis of components in the immune system (Frost and Lang, 2004;Elsasser et al, 2004). In addition, a direct effect of growth hormone (GH) on TNF-α and IL-6 secretion has been shown by in vitro and in vivo studies (Uronen-Hansson et al, 2003;Pagani et al, 2005;Hochdorfer et al, 2011). In the pig, adipose tissue plays a fundamental role in productive and reproductive performance (Hausman et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Anterior pituitary influence on adipokine expression and secretion by porcine adipocytes

Saleri

Cavalli

Martelli

et al. 2016

Animal

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Nutritional stressors may cause negative effects on animal health and growth and lead to significant economic impact. Adipose tissue is an endocrine organ producing, mediators and hormones, called adipokines. They play a dynamic role in body homeostasis and in the regulation of energy expenditure, interacting with feeding behavior, hormones and growth factors. This in vitro study aimed to investigate how nutritional conditions and growth hormone (GH) can influence nitric oxide (NO) production and the expression and secretion of three important adipokines, that is leptin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), by swine adipocytes. In our experimental model, mesenchymal stem cells from omental adipose tissue were induced to adipogenic differentiation. After differentiation, adipocytes were incubated for 24 h (T0) with DMEM/Ham's F12 (group A) or DMEM/Ham's F12 salts (group B), a DMEM/Ham's F12 formulation deprived of nutritional components. Primary adipocyte cells were also co-cultured for 4 h (T + 4) or 12 h (T + 12) with or without anterior pituitary slices. To stimulate GH secretion by pituitary cells, growth hormone releasing hormone at 10 − 8 M was added at the start of the incubation times (4 or 12 h). At T0, T + 4 and T + 12, NO production, leptin, IL-6 and TNF-α expression and secretion were measured. NO increased ( P < 0.05) up to twofold in restricted culture conditions. Deprived medium and coincubation with anterior pituitary positively influenced leptin secretion and expression. TNF-α was expressed and secreted only in deprived culture condition groups (B, B1 and B2). Nutrients availability and pituitary co-culture did not affect IL-6 expression and secretion. Our study shows an endocrine function for porcine adipocytes. In our model, adipocytes readily responded to nutritional inputs by secretion of molecules affecting energy balance. This secretion capacity was modulated by GH. Improving our knowledge of the role of adipocyte in the endocrine system, may lead to a more complete understanding of regulating energy balance in swine.

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Serum cytokine levels in GH-deficient children during substitutive GH therapy

Cited by 28 publications

References 20 publications

GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

Relationship between Growth Hormone and Cytokines in Short Children Undergoing Growth Hormone Stimulation Testing

Anterior pituitary influence on adipokine expression and secretion by porcine adipocytes

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