Randomized, dose‐finding trial of ghrelin treatment for chronic respiratory failure

Miki, Keisuke; Maekura, Ryoji; Nakazato, Masamitsu; Matsumoto, Nobuhiro; Kitada, Shuichi; Miki, Mari; Yoshimura, K.; Mori, Masahide; Kangawa, Kenji

doi:10.1111/crj.12364

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…Kodama and colleagues showed ghrelin to suppress airway inflammation and increase functional exertion capacity in patients with chronic respiratory failure [73]. Miki and colleagues later showed that ghrelin enhanced exercise capacity, expiratory pressure and improved respiratory symptoms in COPD patients [83,243] and showed benefits on exertional dyspnea [244], These effects may be dose-dependent [245,246]. For lung cancer, treatment with the potent ghrelin analog anamorelin has shown benefits on appetite, lean mass retention, performance and quality of life [133,134,135].…”

Section: Pulmonary Diseasementioning

confidence: 99%

Therapeutic Potential of Targeting the Ghrelin Pathway

Colldén

Tschöp

Müller

2017

IJMS

124

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Ghrelin was discovered in 1999 as the endogenous ligand of the growth-hormone secretagogue receptor 1a (GHSR1a). Since then, ghrelin has been found to exert a plethora of physiological effects that go far beyond its initial characterization as a growth hormone (GH) secretagogue. Among the numerous well-established effects of ghrelin are the stimulation of appetite and lipid accumulation, the modulation of immunity and inflammation, the stimulation of gastric motility, the improvement of cardiac performance, the modulation of stress, anxiety, taste sensation and reward-seeking behavior, as well as the regulation of glucose metabolism and thermogenesis. Due to a variety of beneficial effects on systems’ metabolism, pharmacological targeting of the endogenous ghrelin system is widely considered a valuable approach to treat metabolic complications, such as chronic inflammation, gastroparesis or cancer-associated anorexia and cachexia. The aim of this review is to discuss and highlight the broad pharmacological potential of ghrelin pathway modulation for the treatment of anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal (GI) disorders, inflammatory disorders and metabolic syndrome.

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Section: Pulmonary Diseasementioning

confidence: 99%

Therapeutic Potential of Targeting the Ghrelin Pathway

Colldén

Tschöp

Müller

2017

IJMS

124

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“… 24 Recently, Miki and his colleagues further performed a multicenter, randomized, double-blind, placebo-controlled trail, indicating underweight COPD patients benefited from intravenous treatment of high-dose ghrelin (2 µg/kg) twice daily for 3 weeks with improvements in St. George Respiratory Questionnaire score, exercise capacity, ventilatory–cardiac parameters, and exertional cardiac function. 25 – 28 These data further suggest that compensation with exogenous ghrelin may be a potential choice in treatment of underweight COPD patients.…”

Section: Discussionmentioning

confidence: 83%

Elevated circulating ghrelin in patients with COPD: A meta-analysis

Zhang

Yang

Wang³

et al. 2018

Chron Respir Dis

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Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, has been implicated in chronic obstructive pulmonary disease (COPD). Recently, several studies reported inconsistent levels of ghrelin in plasma/serum of COPD patients. This meta-analysis aims to determine the circulating level of ghrelin in COPD. Published case–control or cohort studies were retrieved from Pubmed and Embase databases. Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated in a random-effects model. Nine studies involving 515 subjects were included. Pooled effect size showed that circulating ghrelin levels were significantly enhanced in COPD patients compared with those in controls (SMD: 0.83, 95% CI: 0.04 to 1.62, p = 0.039). Noticeably, five studies stratified for body mass index in COPD group and we further found ghrelin levels were significantly higher in underweight COPD patients than those in normal weight cases (SMD: 1.52, 95% CI: 0.43 to 2.61, p = 0.006). However, no significant difference regarding ghrelin levels was indicated between normal weight COPD and controls (SMD: 0.64, 95% CI: −0.36 to 1.63, p = 0.210). In this meta-analysis, circulating level of ghrelin is significantly elevated in patients with COPD, especially in those underweight, indicating supplement with exogenous ghrelin could be a therapeutic choice for underweight COPD patients.

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“…63,64 In humans, multiple clinical trials for ghrelin have been completed for several disorders, including heart diseases, chronic respiratory failure, weight loss, and inflammation. [65][66][67][68] Exogenous ghrelin treatment significantly suppresses endoplasmic reticulum stress and inflammation-induced testicular dysfunction by regulating the toll-like receptor 4 (TLR4)/ NF-κB signaling pathway in male mice. 69 According to F I G U R E 1 Post-translational processing of ghrelin.…”

Section: Direct Effects Of the Ghrelin Pathway On Inflammation Regula...mentioning

confidence: 99%

“…In vivo, exogenous ghrelin administration prevents cerulein‐induced acute pancreatitis in rats by alleviating pancreatic blood flow; reducing inflammatory factors TNF‐α and interleukin‐1β (IL‐1β); activating IKKβ/NF‐κB signaling, and stimulating pancreatic cell regeneration 63,64 . In humans, multiple clinical trials for ghrelin have been completed for several disorders, including heart diseases, chronic respiratory failure, weight loss, and inflammation 65–68 . Exogenous ghrelin treatment significantly suppresses endoplasmic reticulum stress and inflammation‐induced testicular dysfunction by regulating the toll‐like receptor 4 (TLR4)/NF‐κB signaling pathway in male mice 69 .…”

Section: Direct Effects Of the Ghrelin Pathway On Inflammation Regula...mentioning

confidence: 99%

Potential role of ghrelin in the regulation of inflammation

Zhang

Guo

et al. 2022

The FASEB Journal

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Several diseases are caused or progress due to inflammation. In the past few years, accumulating evidence suggests that ghrelin, a gastric hormone of 28-amino acid residue length, exerts protective effects against inflammation by modulating the related pathways. This review focuses on ghrelin's anti-inflammatory and potential therapeutic effects in neurological, cardiovascular, respiratory, hepatic, gastrointestinal, and kidney disorders. Ghrelin significantly alleviates excessive inflammation and reduces damage to different target organs mainly by reducing the secretion of inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), and inhibiting the nuclear factor kappa-B (NF-κB) and NLRP3 inflammasome signaling pathways.Ghrelin also regulates inflammation and apoptosis through the p38 MAPK/c-Jun N-terminal kinase (JNK) signaling pathway; restores cerebral microvascular integrity, and attenuates vascular leakage. Ghrelin activates the phosphoInositide-3 kinase (PI3K)/protein kinase B (Akt) pathway and inhibits inflammatory responses in cardiovascular diseases and acute kidney injury. Some studies show that ghrelin exacerbates colonic and intestinal manifestations of colitis.Interestingly, some inflammatory states, such as non-alcoholic steatohepatitis, inflammatory bowel diseases, and chronic kidney disease, are often associated with high ghrelin levels. Thus, ghrelin may be a potential new therapeutic target for inflammation-related diseases.

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Randomized, dose‐finding trial of ghrelin treatment for chronic respiratory failure

Abstract: Although the primary outcome of the study was not met, high-dose ghrelin with PR improved exertional cardiac function and blood gas values, and inhibited circulating VEGF-A levels.

Cited by 4 publications

References 34 publications

Therapeutic Potential of Targeting the Ghrelin Pathway

Therapeutic Potential of Targeting the Ghrelin Pathway

Elevated circulating ghrelin in patients with COPD: A meta-analysis

Potential role of ghrelin in the regulation of inflammation

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