Recombinant human growth hormone improves survival and protects against acute lung injury in murine Staphylococcus aureus sepsis

Yi, Cheng; Cao, Yubin; Mao, Shengjun; Liu, H.; Ji, Ling; Xu, Shanshan; Zhang, M.; Huang, Ying

doi:10.1007/s00011-009-0056-0

Cited by 24 publications

(12 citation statements)

References 21 publications

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“…Typically NOX4 is upregulated in cells by SSF, hypoxemia or cytokines like TNF-α, and the latter is usually elevated in patients with ischemic process [141], favoring inflammation and phosphorylation of eNOS, which reduces NO production [142]. In the GHAS trial, GH also significantly reduced circulating levels of TNF-α, which is consistent with other studies [143,144], and with the fact that improves redox balance, representing another way to act in this process (Table 1). TNF-α has other negative actions, elevating intracellular SOCS [106], or diminishing IGF-I or SMCs in the vascular wall [85].…”

Section: Preprintssupporting

confidence: 81%

Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

Caicedo¹,

Devesa²,

Álvarez³

et al. 2019

Preprint

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Despite the important role that the GH/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium has turned to be considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effect, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, it will be described the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy. It will be analyzed all those elements triggering the local and systemic production of GH/IGF-I and their possible role both in physiological and pathological conditions. The whole evidence will be combined with important data from the GHAS trial, in which GH or placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of the ischemic disease.A normal embryonic development needs the formation of blood vessels [21]; after birth there is also the need of the formation of new blood vessels while growing, but also in some physiological processes such as the menstrual cycle in women and the development of the mammary gland during pregnancy [22], but apart from these situations, adult neovascularization rarely takes place and when it happens it is associated with pathological affectations, such as wounds, muscle injuries, fractures or hypoxia/ischemia. The question now would be: how does neovascularization occur in adults and what is the role of the GH / IGF-I system in it?As it seems logical, hypoxia is a very important stimulus for the growth of new blood vessels [23], triggering this growth through hypoxia-inducible factors (HIF) that act on the expression of proangiogenic factors, but also that of anti-angiogenic factors to achieve the perfect number and size of the vessels necessary to compensate for the lack of oxygen supply and to regenerate the tissue [23]. This is a clear and well-established fact for angiogenesis. However, when a progressive narrowing of the vascular lumen appears, preexisting collaterals will have to growth to compensate the lack of distal flow which is triggered in a totally different way. With independence of that, the stimulation of endothelial nitric oxide synthase (eNOS) that leads to the production of nitric oxide (NO) from the vascular endothelium seems to be the key mediator for both kind of reparative processes. NO is a potent vasodilator, therefore increasing blood supply to the zone affected by hypoxia/ischemia. This implies changes in the vascular tone, vasorelaxation and vasopermeability, which are affected in arteries suffering an atherosclerotic damage. Interestingly, GH activates the NO pathway [14,24] throughout direct mechanisms tha...

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Section: Preprintssupporting

confidence: 81%

Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

Caicedo¹,

Devesa²,

Álvarez³

et al. 2019

Preprint

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“…The severity of LPS-induced lung injury was further evaluated. The lung injury score was obtained based on the presence of cell infiltration and accumulation, pulmonary edema, and/or hemorrhage [21]. The lung injury scores of LPS-treated groups were Flavonoid Ameliorates Endotoxemic Lung Injury PLOS ONE | www.plosone.org significantly increased.…”

Section: Oroa Post-treatment Inhibited the Enhanced Lung Injury Scorementioning

confidence: 99%

“…The lung injury scores were estimated based on histological examination, including the hemorrhage of intra-alveolar septa, cell infiltration, and lung wet-to-dry ratio. The scores were determined as 0 (no injury), 1 (10-20% severity), 2 (20-40% severity), 3 (40-50% severity), or 4 (greater than 50% severity) [21]. The degree of intra-alveolar septa hemorrhage was scored as 0 (no hemorrhage), 1 (mild hemorrhage), or 2 (severe hemorrhage).…”

Section: Lung Injury Assessmentmentioning

confidence: 99%

Oroxylin-A Rescues LPS-Induced Acute Lung Injury via Regulation of NF-κB Signaling Pathway in Rodents

et al. 2012

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Background and PurposeSuccessful drug treatment for sepsis-related acute lung injury (ALI) remains a major clinical problem. This study was designed to assess the beneficial effects of post-treatment of oroxylin A (OroA), a flavonoid, in ameliorating lipopolysaccharides (LPS)-induced lung inflammation and fatality.Experimental ApproachRats were injected with LPS (10 mg/kg, iv) to induce ALI, and OroA was given (15 mg/kg, iv) 1 hr or 6 hrs after LPS challenge. Twenty four hrs after LPS challenge, biochemical changes in the blood and lung tissues, and morphological/histological alterations in the lung associated with inflammation and injury were examined. Therapeutic effect of OroA was assessed by measuring the survival rate in endotoxemic mice.Key ResultsLPS (10 mg/kg, iv) significantly altered WBC counts, elevated plasma tumor necrosis factor (TNF)-α and nitric oxide (NO), increased pulmonary edema, thickened alveolar septa, and decreased survival rate. These changes were ameliorated by OroA (15 mg/kg, iv) administered 1 hr or 6 hrs after LPS challenge. This post-treatment also significantly attenuated LPS-induced activation of nuclear factor-κB (NF-κB) and the release of high mobility group box 1 (HMGB1) in lung tissues. Furthermore, post-treatment with OroA (60 mg/kg, ip) administered 1 hr or 6 hrs after LPS challenge in mice significantly increased survival rate.Conclusion and ImplicationOroA administered after induction of ALI by LPS significantly prevent and revere lung tissues injuries with increased survival rate. Positive post-treatment effects of OroA suggest that OroA is a potentially useful candidate for managing lung inflammation in LPS-induced endotoxemia and septic shock.

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“…Moreover, the available evidence is controversial with reported examples of both anti- and pro-inflammatory effects of GH. Growth hormone therapy can reduce the levels of C-reactive protein (CRP), an important marker of inflammation in GH-deficient patients (16), and exert anti-inflammatory effects in different models of experimentally induced sepsis by reducing the levels of TNFα and promoting secretion of IL-10 (17, 18). Perhaps exogenous GH can overcome the effects of sepsis-induced IGF-1 resistance (19).…”

mentioning

confidence: 99%

Growth hormone, inflammation and aging

Masternak¹,

Bartke²

2012

Pathobiology of Aging & Age-related Diseases

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Mutant animals characterized by extended longevity provide valuable tools to study the mechanisms of aging. Growth hormone and insulin-like growth factor-1 (IGF-1) constitute one of the well-established pathways involved in the regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH deficiency as well as growth hormone receptor/growth hormone binding protein knockout (GHRKO) mice characterized by GH resistance live significantly longer than genetically normal animals. During normal aging of rodents and humans there is increased insulin resistance, disruption of metabolic activities and decline of the function of the immune system. All of these age related processes promote inflammatory activity, causing long term tissue damage and systemic chronic inflammation. However, studies of long living mutants and calorie restricted animals show decreased pro-inflammatory activity with increased levels of anti-inflammatory adipokines such as adiponectin. At the same time, these animals have improved insulin signaling and carbohydrate homeostasis that relate to alterations in the secretory profile of adipose tissue including increased production and release of anti-inflammatory adipokines. This suggests that reduced inflammation promoting healthy metabolism may represent one of the major mechanisms of extended longevity in long-lived mutant mice and likely also in the human.

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Recombinant human growth hormone improves survival and protects against acute lung injury in murine Staphylococcus aureus sepsis

Cited by 24 publications

References 21 publications

Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

Oroxylin-A Rescues LPS-Induced Acute Lung Injury via Regulation of NF-κB Signaling Pathway in Rodents

Growth hormone, inflammation and aging

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