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

Abstract

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.

Adipose tissue loss in adjuvant arthritis is associated with a decrease in lipogenesis, but not with an increase in lipolysis

“…The decrease in serum leptin and its gene expression in arthritic rats has previously been described in different models of experimental arthritis (Hultgren & Tarkowski 2001, Granado et al 2005a, Stofkova et al 2006. A decrease in leptin secretion has also been reported in humans with other chronic inflammatory illnesses, such as tuberculosis or inflammatory bowel disease (van Crevel et al 2002, Karmiris et al 2006.…”

Ghrelin Improves Antioxidant Defense in Blood and Brain in Normobaric Hypoxia in Adult Male Rats

“…18 In addition, ghrelin has several antiinflammatory properties and decreases neuronal apoptosis. [19][20][21][22] Antioxidant properties of ghrelin have also been demonstrated in recent studies. [23][24][25] Therefore, the aim of this study was to evaluate the effects of ghrelin on the blood levels of MDA and TAC and brain levels of MDA, SOD, GPx and CAT in the normobaric systemic hypoxia situation in rats.…”

Ghrelin treatment protects lactotrophs from apoptosis in the pituitary of diabetic rats

“…Similarly, ghrelin has been reported to decrease nitric oxide production by peritoneal macrophages (Granado et al, 2005) and to decrease high glucose-induced apoptosis of endothelial cells and apoptosis induced by oxygen-glucose deprivation in hypothalamic neuronal cells through reactive oxygen species inhibition (Chung et al, 2007;Zhao et al, 2007). Moreover, it has recently been reported that UCP2 mediates ghrelin's orexigenic effect on NPY/AgRP neurons by lowering free radicals (Andrews et al, 2008).…”

“…In addition, anti-inflammatory and anti-apoptotic actions of ghrelin have been reported in different organs and tissues Dixit et al, 2004;Granado et al, 2005;Granata et al, 2006).…”