Background: Weight loss in cystic fibrosis (CF) may be associated with altered levels of appetite stimulating peptide ghrelin and the appetite decreasing peptide leptin. However, prior data oil leptin in CF are conflicting, while the data on ghrelin are scarce. We hypothesized that weight loss in CF is associated with low levels ghrelin and elevated levels of leptin. Methods: Plasma ghrelin, leptin, TNF-alpha, IL-1 and IL-6, BMI, fat free mass (FFM), fat mass (FM) were measured in 74 CF adults and 20 controls. CF subjects were divided into 3 groups based on lung disease: mild (n = 19), moderate (n = 30) and severe (n = 25). Results: Severe CF patients (% predicted FEVI 27 +/- 7, median BMI 21 kg/m(2)) had significantly elevated ghrelin and decreased leptin compared to controls and other CF Subjects. Ghrelin correlated (r value, P value) with BMI (-0.35,<0.001), FFM (-0.22,<0.05), FM (-0.41,<0.0001), FEVI (-0.62,<0.001), TNF-alpha (0.51,<0.0001), IL-1 (0.56,<0.0001), and IL-6(0.33,<0.01). Leptin correlated (r value, p value) with BMI (0.40,<0.0001), FM (0.56,<0.0001) FEVI (0.34,<0.05), IL-1 (-0.51,<0.05) and TNF-alpha (-0.43,<0.0001). BMI and FEVI were independent predictors of ghrelin (-0.35 <0.05:-0.59,<0.001). FM was a predictor of leptin (0.56,<0.0001). Cytokines were elevated only in severe CF (severe CF vs. controls, pg/ml): TNF-alpha (3.4 +/- 0.6 vs. 1.2 +/- 0.4), IL-1 (3.5 +/- 1 vs. 0.2 +/- 0.1), IL-6 (17.4 +/- 4 vs. 2.4 +/- 2). Conclusions: Elevated ghrelin and decreased leptin levels are a consequence rather than a cause of weight loss in advanced CF. (C) 2008 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.