Regulation and prognostic relevance of serum ghrelin concentrations in critical illness and sepsis

Introduction: Ghrelin has been recently identified as a mediator of various beneficial effects in animal models of sepsis. At present, no data are available concerning specific properties of ghrelin in critically ill patients from large cohorts. In order to identify possible pathogenic functions of ghrelin in critically ill patients and human sepsis from a clinical point of view, we aimed at analyzing ghrelin serum concentrations in a large cohort of well characterized patients with critical illness. Methods: A total of 170 critically ill patients (122 with sepsis, 48 without sepsis) were studied prospectively on admission to the Medical intensive care unit (ICU) and compared to 60 healthy controls. Careful assessment of clinical data, various laboratory parameters, metabolic and endocrine functions as well as investigational inflammatory cytokine profiles have been performed, and patients were followed for approximately three years. Results: Ghrelin serum concentrations are elevated in critically ill patients as compared to healthy controls, but do not differ between sepsis and non-sepsis patients. The underlying etiologies of critical diseases are not associated with ghrelin serum levels. Neither pre-existing diabetes mellitus nor body mass index is correlated to serum ghrelin concentrations. Ghrelin is not correlated to markers of inflammation or hepatic function in critically ill patients. In the subgroup of non-sepsis patients, ghrelin correlates inversely with renal function and markers of carbohydrate metabolism. High ghrelin levels are an indicator for a favourable prognosis concerning mortality at the ICU in sepsis patients. Furthermore, ghrelin is significantly associated with the necessity of ventilation in critically ill patients. Conclusions: Ghrelin serum concentrations are elevated in all circumstances of critical disease, including sepsis and non-sepsis patients. High ghrelin levels are a positive predictor of ICU-survival in sepsis patients, matching previous results from animal models. Future experimental and clinical studies are needed to evaluate ghrelin as a novel prognostic tool in ICU patients and its potential therapeutic use in sepsis.