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.
Highlights
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection [1] which continues to be a leading cause of death in the United States
Ghrelin was discovered to downregulate the expression of pro-inflammatory cytokines such as tumor necrosis factor a (TNF-a), interleukin (IL)-6, and IL-1b [4], Ghrelin as an Anti-Sepsis Peptide while upregulating the expression of anti-inflammatory cytokines e.g., IL-10 and transforming growth factor (TGF) b [6]
In sepsis, when the host immune system is activated by pathogen-associated molecular patterns (PAMPs) or damageassociated molecular patterns (DAMPs), a cascade of intracellular signal transduction pathways are stimulated, which lead to the activation of downstream transcription factor NF-kB and mitogen-activated protein kinase (MAPK)
Summary
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection [1] which continues to be a leading cause of death in the United States. The beneficial role of ghrelin in downregulating the expression of proinflammatory cytokines was reported in several studies [4, 5] the mechanism of action of ghrelin in sepsis has only been clarified within the last few years. A peptide hormone, is widely recognized as a growth hormone secretagogue [7] and independently acts as an appetite stimulant. Besides these classic well-established roles of ghrelin, it has been shown to affect many organ systems including the central nervous system as well the cardiovascular, gastrointestinal, reproductive, and immune systems (Tables 1 and 2). We focus on the role of ghrelin in inflammation and its emerging usefulness in the treatment of sepsis
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