Abstract

Background: In a rat model, ghrelin has been shown to exert an anti-inflammatory effect in cardiovascular disease and arthritis. It also inhibits expression of proinflammatory cytokines. The wide tissue distribution of ghrelin expression and the presence of growth hormone secretagogue receptor (GHS-R) in the lung suggest that ghrelin may be a potential signal modulator in the lung. However, whether ghrelin exerts anti-inflammatory effects on acute lung injury induced by lipopolysaccharide (LPS) remains unknown. Therefore, we sought to investigate the role of ghrelin in LPS-induced acute lung injury and its underlying mechanism.
Material/Methods: We induced acute lung injury in rats via intratracheal instillation of LPS. We injected ghrelin and Nomega-nitro-L-arginine methyl ester (L-NAME) through the tail vein. Lung injury was assessed by histologic examination 6 hours after injury. Lung macrophages were isolated and incubated with LPS, L-NAME, and ghrelin. Concentrations of TNF-alpha and IL-1beta in bronchoalveolar lavage (BAL) fluid and culture supernatant were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) in BAL fluid and culture supernatant and NO synthase (NOS) in cultured macrophage were detected by a spectrophotometry.
Results: Ghrelin attenuated pulmonary inflammation in LPS-induced acute lung injury, decreased production of proinflammatory cytokines, and increased NO concentrations in BAL fluid. Ghrelin also suppressed LPS-induced expression of proinflammatory cytokines, and increased NOS activity in cultured macrophages and NO concentrations in culture supernatants. The anti-inflammatory effect of ghrelin was inhibited by L-NAME.
Conclusions: Ghrelin attenuates LPS-induced acute lung inflammation and suppresses LPS-induced proinflammatory cytokine production in lung macrophages, which is partially mediated by increased NO production.

Keywords: Ghrelin, acute lung injury, Nitric Oxide, Animals, Bronchoalveolar Lavage Fluid, Culture Media, Cytokines - biosynthesis, Ghrelin - pharmacology, Inflammation Mediators - metabolism, Lipopolysaccharides - pharmacology, Macrophages, Alveolar - enzymology, Nitric Oxide - metabolism, Nitric Oxide Synthase - metabolism, Rats, Rats, Sprague-Dawley, Respiratory Distress Syndrome, Adult - prevention & control