I Nikitopoulou1, E Kampisiouli2, E Jahaj2, A G Vassiliou1, I Dimopoulou2, Z Mastora2, S Tsakiris1, K Perreas1, M Tzanela3, C Routsi2, S E Orfanos4, A Kotanidou5. 1. GP Livanos and M Simou Laboratories, 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece. 2. 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece. 3. Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece. 4. GP Livanos and M Simou Laboratories, 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece; 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece; 2nd Department of Critical Care, Medical School, National & Kapodistrian University of Athens, "Attikon" Hospital, Haidari, Athens, Greece. Electronic address: stylianosorfanosuoa@gmail.com. 5. GP Livanos and M Simou Laboratories, 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece; 1st Department of Critical Care & Pulmonary Services, Medical School, National & Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece.
Abstract
BACKGROUND: Ghrelin is a hormone mainly produced by cells of the gastric mucosa, which has been shown to possess anti-inflammatory and immunomodulatory properties. The objective of the study was to investigate ghrelin levels during sepsis, as well as in an experimental sepsis model. METHODS: All consecutive admissions to the ICU of a tertiary hospital in Athens, Greece were screened for eligibility during the study. Thirty four non-septic patients upon ICU admission who subsequently developed sepsis were enrolled. Clinical data and scores were recorded, and blood samples were obtained at baseline (upon ICU admission), and at sepsis development. Total and active ghrelin, leptin, and cytokines were measured. Moreover, lipopolysaccharide (LPS) was administered to mice in order to induce endotoxemia and at specified time points, blood and tissue samples were collected. RESULTS: In patients, serum total and active ghrelin concentrations were significantly elevated in sepsis compared to baseline (553.8 ± 213.4 vs 193.5 ± 123.2, p < 0.001; 254.3 ± 70.6 vs 56.49 ± 16.3, p < 0.001). Active ghrelin levels at the sepsis stage were inversely correlated with SOFA score and length of stay in the ICU (p = 0.023 and p = 0.027 respectively). In the mouse endotoxemia model ghrelin levels were elevated following LPS treatment, and the same trend was observed for leptin, TNFα and IL-6. Ghrelin administration managed to reduce IL-6 levels in mouse serum and in BALF. Pulmonary expression of ghrelin and its receptor GHSR1a was found decreased in LPS-treated mice. CONCLUSIONS: In a well-defined cohort of ICU patients, we have demonstrated that active and total ghrelin increase in sepsis. The same is true for the experimental sepsis model used in the study. The inverse correlation of active ghrelin levels with SOFA score and length of ICU stay among septic patients is indicative of a potential protective role of active ghrelin during the septic process.
BACKGROUND:Ghrelin is a hormone mainly produced by cells of the gastric mucosa, which has been shown to possess anti-inflammatory and immunomodulatory properties. The objective of the study was to investigate ghrelin levels during sepsis, as well as in an experimental sepsis model. METHODS: All consecutive admissions to the ICU of a tertiary hospital in Athens, Greece were screened for eligibility during the study. Thirty four non-septic patients upon ICU admission who subsequently developed sepsis were enrolled. Clinical data and scores were recorded, and blood samples were obtained at baseline (upon ICU admission), and at sepsis development. Total and active ghrelin, leptin, and cytokines were measured. Moreover, lipopolysaccharide (LPS) was administered to mice in order to induce endotoxemia and at specified time points, blood and tissue samples were collected. RESULTS: In patients, serum total and active ghrelin concentrations were significantly elevated in sepsis compared to baseline (553.8 ± 213.4 vs 193.5 ± 123.2, p < 0.001; 254.3 ± 70.6 vs 56.49 ± 16.3, p < 0.001). Active ghrelin levels at the sepsis stage were inversely correlated with SOFA score and length of stay in the ICU (p = 0.023 and p = 0.027 respectively). In the mouseendotoxemia model ghrelin levels were elevated following LPS treatment, and the same trend was observed for leptin, TNFα and IL-6. Ghrelin administration managed to reduce IL-6 levels in mouse serum and in BALF. Pulmonary expression of ghrelin and its receptor GHSR1a was found decreased in LPS-treated mice. CONCLUSIONS: In a well-defined cohort of ICU patients, we have demonstrated that active and total ghrelin increase in sepsis. The same is true for the experimental sepsis model used in the study. The inverse correlation of active ghrelin levels with SOFA score and length of ICU stay among septic patients is indicative of a potential protective role of active ghrelin during the septic process.