Ghrelin as an Anti-Sepsis Peptide: Review

Abstract

Sepsis continues to produce widespread inflammation, illness, and death, prompting intensive research aimed at uncovering causes and therapies. In this article, we focus on ghrelin, an endogenous peptide with promise as a potent anti-inflammatory agent. Ghrelin was discovered, tracked, and isolated from stomach cells based on its ability to stimulate release of growth hormone. It also stimulates appetite and is shown to be anti-inflammatory in a wide range of tissues. The anti-inflammatory effects mediated by ghrelin are a result of both the stimulation of anti-inflammatory processes and an inhibition of pro-inflammatory forces. Anti-inflammatory processes are promoted in a broad range of tissues including the hypothalamus and vagus nerve as well as in a broad range of immune cells. Aged rodents have reduced levels of growth hormone (GH) and diminished immune responses; ghrelin administration boosts GH levels and immune response. The anti-inflammatory functions of ghrelin, well displayed in preclinical animal models of sepsis, are just being charted in patients, with expectations that ghrelin and growth hormone might improve outcomes in patients with sepsis.

Protective and Healing Effects of Ghrelin and Risk of Cancer in the Digestive System

“…Anti-inflammatory effects play an essential role in protective and therapeutic effect of ghrelin in the gut. Ghrelin exhibits anti-inflammatory effects by the inhibition of proinflammatory processes and the stimulation of anti-inflammatory processes [ 149 ]. Numerous experimental studies indicate that administration of ghrelin inhibits the expression, synthesis, and release of proinflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α).…”

“…The development and progress of inflammation is related to the activation of the nuclear factor-κB (NF-κB) proinflammatory signaling pathway [ 156 ]. The binding of IL-1β and TNF-α to IL-1 and TNF receptor, respectively, as well as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) to pattern recognition receptors (PRRs), especially Toll-like receptors (TLRs), leads to the activation of downstream transcription factor NF-κB and mitogen-activated protein kinase (MAPK) [ 149 , 156 ]. NF-κB is a protein complex, including, NF-κB2 p52/p100, NF-κB1 p50/p105, c-Rel, RelA/p65, and RelB.…”

“…Next, IKK phosphorylates IκBα protein, resulting in dissociation of IκBα from NF-κB. Active NF-κB complexes translocate into the nucleus and induce the expression of target genes [ 149 ].…”

“…Previous studies showed that ghrelin inhibits the translocation of NF-κB into the nucleus, leading to suppression of proinflammatory cytokine production [ 120 , 145 , 149 , 157 ].…”

GIST and Ghrelin: To Be or Not to Be?

“…Ghrelin is the ligand of the growth hormone secretagogue receptor [27] and has both peripheral and central action [28], with a wide array of effects in both physiological and pathological settings [28,29]. Its role is not only linked to energy metabolism and appetite control [30][31][32] but also inflammation and oxidative stress [33,34], the modulation of cardiac activity and post-injury myocardial changes [35,36], stress and anxiety [37,38], anorexia and other psychiatric conditions [39,40], neurodegenerative disorders [41] and sepsis [42,43]. The longstanding contribution of ghrelin to carcinogenesis and tumor progression, especially in GIT malignancies [44,45] has been demonstrated through positive IHC and mRNA expression in endocrine and non-endocrine tumors [46,47] spanning across a multitude of organs and systems [45].…”