Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats

• Published in: American journal of physiology: endocrinology and metabolism Vol. 288; no. 3; pp. E486 - E492
• Main Authors: Granado, Miriam, Priego, Teresa, Martin, Ana I, Villanua, M. Angeles, Lopez-Calderon, Asuncion
• Format: Journal Article
• Language: English
• Published: United States 01.03.2005
• Subjects: Adrenocorticotropic Hormone - blood; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Arthritis, Experimental - drug therapy; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Blood - drug effects; Body Weight - drug effects; Body Weight - physiology; Corticosterone - blood; Eating - drug effects; Eating - physiology; Foot - pathology; Freund's Adjuvant - immunology; Freund's Adjuvant - pharmacology; Ghrelin; Inflammation - drug therapy; Interleukin-6 - blood; Leptin - blood; Lipopolysaccharides - pharmacology; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Male; Nitrates - blood; Nitrates - metabolism; Nitrites - blood; Nitrites - metabolism; Oligopeptides - pharmacology; Oligopeptides - therapeutic use; Peptide Hormones - agonists; Peptide Hormones - blood; Peptide Hormones - pharmacology; Rats; Rats, Wistar
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00196.2004

1 Departamento Fisiología, Facultad de Medicina, Universidad Complutense, Madrid; and 2 Departamento Ciencias Morfológicas y Fisiología, Universidad Europea, Madrid, Spain Submitted 3 May 2004 ; accepted in final form 21 October 2004 Chronic arthritis induces hypermetabolism and cachexia. Ghrelin is a gastrointestinal hormone that has been proposed as a treatment to prevent cachexia. The aim of this work was to examine the effect of administration of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) to arthritic rats. Male Wistar rats were injected with Freund’s adjuvant, and 15 days later arthritic and control rats were daily injected with GHRP-2 (100 µg/kg) or with saline for 8 days. Arthritis induced an increase in serum ghrelin ( P < 0.01) and a decrease in serum concentrations of leptin ( P < 0.01), whereas GHRP-2 administration increased serum concentrations of leptin. GHRP-2 increased food intake in control rats but not in arthritic rats. However, in arthritic rats GHRP-2 administration ameliorated the external symptoms of arthritis, as it decreased the arthritis score (10.4 ± 0.8 vs. 13.42 ± 0.47, P < 0.01) and the paw volume. In addition, circulating IL-6 and nitrites/nitrates were increased by arthritis, and GHRP-2 treatment decreased the serum IL-6 levels ( P < 0.01). To elucidate whether GHRP-2 is able to modulate IL-6 release directly on immune cells, peritoneal macrophage cultures were incubated with GHRP-2 or ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor. Both GHRP-2 (10 –7 M) and ghrelin (10 –7 M) prevented endotoxin-induced IL-6 and decreased nitrite/nitrate release from peritoneal macrophages in vitro. These data suggest that GHRP-2 administration has an anti-inflammatory effect in arthritic rats that seems to be mediated by ghrelin receptors directly on immune cells. interleukin-6; inflammation Address for reprint requests and other correspondence: A. López-Calderón, Dpt Fisiología, Fac Medicina, Univ Complutense, 28040 Madrid, Spain (E-mail: ALC{at}med.ucm.es )