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Rheumatology Advance Access originally published online on November 17, 2003
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Rheumatology 2004; 43: 306-310
Rheumatology Vol. 43 No. 3 (c) British Society for Rheumatology 2003; all rights reserved


Concise report

Chronic inflammation modulates ghrelin levels in humans and rats

M. Otero, R. Nogueiras3, F. Lago1, C. Dieguez3, J. J. Gomez-Reino2 and O. Gualillo

Research Laboratory 4 and 1Laboratory 1, Santiago University Clinical Hospital, Santiago de Compostela, 2Rheumatology Unit, Santiago University Clinical Hospital and Department of Medicine, University of Santiago de Compostela and 3Department of Physiology, University of Santiago de Compostela, Spain.

Correspondence to: O. Gualillo, Santiago University Clinical Hospital, Research Area, Research Laboratory 4, Trav. Choupana Sn, 15706 Santiago de Compostela, Spain. E-mail: gualillo{at}usc.es

Objectives. The aim of this work was to investigate whether changes in plasma ghrelin, the recently discovered 28-amino acid gastric hormone that regulates growth hormone (GH) secretion and energy homeostasis, occur during inflammation in adjuvant-induced arthritis (AA) in rats. For completeness, ghrelin plasma levels were measured in rheumatoid arthritis (RA) patients.

Methods. AA was induced in male Lewis rats using Freund's complete adjuvant. Animals were monitored for weight and food intake, every 2 or 3 days, along all time-course experiments. Plasma ghrelin concentrations in 31 RA patients and 18 healthy controls, as well as in rats, were determined by a specific double-antibody radioimmunoassay. Gastric ghrelin mRNA expression was evaluated by northern blot analysis. Human GH and insulin-like growth factor (IGF)-1 were determined by quantitative chemiluminescence assay.

Results. Compared with controls, arthritic rats gained significantly (P < 0.01) less body weight than controls until the end of the study, when a partial recovery occurred. Ghrelin plasma levels were significantly lower at day 7 after arthritis induction than in controls (AA 7 = 91.2 ± 5.6 pg/ml vs controls = 124.75 ± 5.9 pg/ml), but they recovered to control levels by day 15. RA patients had ghrelin plasma levels significantly lower than healthy controls (RA = 24.54 ± 2.57 pg/ml vs 39.01 ± 4.47 pg/ml of healthy controls; P = 0.0041).

Conclusion. In AA, there is a compensatory variation of ghrelin levels that relates to body weight adjustments. Recovery of ghrelin levels in the latter stage suggests an adaptive response and may represent a compensatory mechanism under catabolic conditions. In RA patients, chronic imbalance in ghrelin levels suggests that this gastric hormone may participate, together with other factors, in alterations of metabolic status during inflammatory stress.

KEY WORDS: Ghrelin, Rheumatoid arthritis, Inflammation experimental models.


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