Growth hormone modulates IL-  and IFN-  release by murine splenocytes activated by LPS or porins of Salmonella Typhimurium

Sommese, Linda; Donnarumma, Giovanna; L'ero, G. Cipollaro De; Marcatili, Antonella; Vitiello, Mariateresa; Galdiero, Massimiliano

doi:10.1099/00222615-45-1-40

Cited by 11 publications

(3 citation statements)

References 30 publications

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“…The present finding of a pronounced decrease of CD4+ cells producing IFN-g after administration of GH Ab adds support to the notion that GH release during sleep fosters type1 cytokine activity [20][21][22][23]33]. However, our findings contrast with some observations showing that GH decreases also production of IL-4 in long-term culture [21,22].…”

Section: Discussionsupporting

confidence: 79%

Sleep-like concentrations of growth hormone and cortisol modulate type1 and type2 in-vitro cytokine production in human T cells

Lange

Dimitrov

Fehm

et al. 2006

International Immunopharmacology

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Section: Discussionsupporting

confidence: 79%

Sleep-like concentrations of growth hormone and cortisol modulate type1 and type2 in-vitro cytokine production in human T cells

Lange

Dimitrov

Fehm

et al. 2006

International Immunopharmacology

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“…For example, pretreatment of rats with growth hormone, but not IGF-I, increases plasma interferon-Á following injection of endotoxin [56]. When human peripheral blood mononuclear cells [57] or murine splenocytes [58] are treated with growth hormone in vitro, there is also an increase in interferon-Á following activation with either allogeneic mononuclear cells or S. typhimurium, respectively.…”

Section: Deficient Myeloid Cell Activation In Aged Subjects: Reversalmentioning

confidence: 99%

The Immune-Endocrine Loop during Aging: Role of Growth Hormone and Insulin-Like Growth Factor-I

Burgess

Liu

Zhou

et al. 1999

Neuroimmunomodulation

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Why a primary lymphoid organ such as the thymus involutes during aging remains a fundamental question in immunology. Aging is associated with a decrease in plasma growth hormone (somatotropin) and IGF-I, and this somatopause of aging suggests a connection between the neuroendocrine and immune systems. Several investigators have demonstrated that treatment with either growth hormone or IGF-I restores architecture of the involuted thymus gland by reversing the loss of immature cortical thymocytes and preventing the decline in thymulin synthesis that occurs in old or GH-deficient animals and humans. The proliferation, differentiation and functions of other components of the immune system, including T and B cells, macrophages and neutrophils, also demonstrate age-associated decrements that can be restored by IGF-I. Knowledge of the mechanism by which cytokines and hormones influence hematopoietic cells is critical to improving the health of aged individuals. Our laboratory has recently demonstrated that IGF-I prevents apoptosis in promyeloid cells, which subsequently permits these cells to differentiate into neutrophils. We also demonstrated that IL-4 acts much like IGF-I to promote survival of promyeloid cells and to activate the enzyme phosphatidylinositol 3′-kinase (PI 3-kinase). However, the receptors for IGF-I and IL-4 are completely different, with the intracellular β chains of the IGF receptor possessing intrinsic tyrosine kinase activity and the α and γc subunit of the heterodimeric IL-4 receptor utilizing the Janus kinase family of nonreceptor protein kinases to tyrosine phosphorylate downstream targets. Both receptors share many of the components of the PI 3-kinase signal transduction pathway, converging at the level of insulin receptor substrate-1 or insulin receptor subtrate-2 (formally known as 4PS, or IL-4 Phosphorylated Substrate). Our investigations with IGF-I and IL-4 suggest that PI 3-kinase inhibits apoptosis by maintaining high levels of the anti-apoptotic protein Bcl-2. The sharing of common activation molecules, despite vastly different protein structures of their receptors, forms a molecular explanation for the possibility of cross talk between IL-4 and IGF-I in regulating many of the events associated with hematopoietic differentiation, proliferation and survival.

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“…GH enhanced cytokine responses and improved the survival of septic mice (28), in contrast to the previously discussed increase in mortality seen in other animal models (4). In studies of splenic lymphocytes GH at an extremely high-dose (10,000 ng/mL) increased cell proliferation and production of IFN␥ in mice with burn injury (29), and GH at a very low dose (0.1 ng/mL) reduced the IFN␥ response to treatment with staphylococcal A toxin (30), but increased the response to a very high-dose of lipopolysaccharide (500 ng/mL) (31). In human PBMCs a very high-dose of GH (500 ng/mL) inhibited the production of TNF␣ in response to a very high-dose of endotoxin (10 ng/mL).…”

Section: Discussionmentioning

confidence: 98%

High-Dose Growth Hormone Does Not Affect Proinflammatory Cytokine (Tumor Necrosis Factor-α, Interleukin-6, and Interferon-γ) Release from Activated Peripheral Blood Mononuclear Cells or after Minimal to Moderate Surgical Stress*

Zarkesh-Esfahani

Kolstad

Metcalfe

et al. 2000

The Journal of Clinical Endocrinology &Amp; Metabolism

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High-dose GH therapy, with GH doses 10 -20 times the normal replacement dose for GH-deficient adults, has been used as an anticatabolic agent in a number of different patient groups. A recent study, however, has shown an increase in mortality in critically ill patients treated with high-dose GH. The increased mortality was associated with multiorgan failure, septic shock, and uncontrolled infection, suggesting that GH may have altered the immune response. The GH receptor and GH are both expressed in peripheral blood mononuclear cells (PBMCs); thus, GH could act as either an endocrine or an autocrine modulator of the immune response. We have examined the hypothesis that high-dose GH therapy may induce proinflammatory cytokines, which are implicated in septic shock. To do this we measured cytokine production by PBMCs incubated in conditions that simulated high-dose GH therapy, and we measured cytokine levels in patients undergoing laparoscopic cholecystectomy who were randomized to receive either high-dose GH therapy (13 IU/m 2 ⅐day) or placebo.To confirm the biological activity of GH in our cell culture system we used a Stat5 functional assay. In this assay GH induced a bellshaped curve, with a maximal response at GH levels between 100-1000 ng/mL. PBMCs from healthy volunteers were incubated with GH in doses from 1-1000 ng/mL for 6 -72 h under resting conditions and after activation with endotoxin and the mixed lymphocyte reaction. Studies were repeated with PBMCs from six individuals using a GH dose of 100 ng/mL (the level of GH found after high-dose GH therapy) and an endotoxin dose that gave a submaximal response (0.01 ng/mL). GH had no effect on cell proliferation or the production of tumor necrosis factor-␣ (TNF␣), interleukin-6 (IL-6), or interferon-␥ (IFN␥). In patients undergoing laparoscopic cholecystectomy there was a time-related effect of surgery on cytokine levels. There was a rise in IL-6 and a fall in TNF␣ at 24 h after surgery; however, high-dose GH therapy had no effect on the cytokine response. We considered the possibility that endogenous GH production by PBMCs could influence the cytokine response in activated PBMCs; however, incubation of PBMCs in the presence of the GH receptor antagonist, B2036, had no effect on TNF␣, IL-6, or IFN␥ production by PBMCs in either the mixed lymphocyte reaction or when activated by endotoxin.These results suggest that high-dose GH therapy does not alter the proinflammatory cytokine response to surgery or endotoxin. The results do not exclude an effect of GH on the immune response, but they suggest that the mortality seen in critically ill patients may be due to factors other than immune modulation. (J Clin Endocrinol Metab 85: 3383-3390, 2000)

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Growth hormone modulates IL- and IFN- release by murine splenocytes activated by LPS or porins of Salmonella Typhimurium

Cited by 11 publications

References 30 publications

Sleep-like concentrations of growth hormone and cortisol modulate type1 and type2 in-vitro cytokine production in human T cells

Sleep-like concentrations of growth hormone and cortisol modulate type1 and type2 in-vitro cytokine production in human T cells

The Immune-Endocrine Loop during Aging: Role of Growth Hormone and Insulin-Like Growth Factor-I

High-Dose Growth Hormone Does Not Affect Proinflammatory Cytokine (Tumor Necrosis Factor-α, Interleukin-6, and Interferon-γ) Release from Activated Peripheral Blood Mononuclear Cells or after Minimal to Moderate Surgical Stress*

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