Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats.
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 microg/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.
Granado
Miriam
M
Dpt Fisiología, Fac Medicina, Univ Complutense, 28040 Madrid, Spain.
Priego
Teresa
T
Martín
Ana I
AI
Villanúa
M Angeles
MA
López-Calderón
Asunción
A
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001769:Blood / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005528:Foot / Q000473:pathology; D005620:Freund's Adjuvant / Q000276:immunology / Q000494:pharmacology; D054439:Ghrelin; D007249:Inflammation / Q000188:drug therapy; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D036361:Peptide Hormones / Q000819:agonists* / Q000097:blood / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D054439:Ghrelin; D015850:Interleukin-6; D020738:Leptin; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009842:Oligopeptides; D036361:Peptide Hormones; D000324:Adrenocorticotropic Hormone; D005620:Freund's Adjuvant; C091874:growth hormone-releasing peptide-2; D003345:Corticosterone