Ghrelin, the gut-brain peptide recently identified as the natural endogenous ligand for growth hormone secretagogue receptors, exerts various endocrine and non-endocrine effects, including control of food intake and energy homeostasis.¹ It could also play a role in modulating immune responses and inflammatory processes.¹ Indeed, ghrelin exerts potent anti-inflammatory effects in vitro and in vivo,^1–5 and high circulating ghrelin levels have been found in rats with septic shock, cysteamine induced duodenal ulcers, and adjuvant induced arthritis.^4–6 Also, we have recently demonstrated that in patients with newly diagnosed coeliac disease, circulating ghrelin levels are abnormally high, correlate positively with intestinal mucosal lesion severity, and normalise in successfully gluten free diet treated patients.⁷ However, normal or even decreased ghrelin levels have been found in other inflammatory diseases, including rheumatoid arthritis and Helicobacter pylori associated gastritis.^8,9

No data on ghrelin pattern are available in inflammatory bowel disease (IBD). Therefore, we evaluated fasting serum total ghrelin levels and the inflammatory markers, tumour necrosis factor α (TNF-α) and C reactive protein (CRP), in 96 consecutive IBD patients and 40 healthy controls (table 1).

The IBD group included 53 ulcerative colitis (UC) patients (27 with active disease, 26 in remission) and 43 Crohn’s disease (CD) patients (15 with active disease, 28 in remission). Serum ghrelin was measured by radioimmunoassay, as previously described,⁷ and TNF-α by a highly sensitive immunoassay (Quantikine HS; R&D Systems, USA). Results were evaluated by one way analysis of variance, followed by the Student-Newman-Keuls multiple comparison test, univariate linear regression, and multiple regression analysis. Results are summarised in table 1.

There were no age or sex related differences for each variable in any group. Patients with active IBD had a normal body mass index and high serum CRP and TNF-α levels (p<0.001 v controls and inactive IBD). TNF-α pattern was similar in UC and CD patients (fig 1A).

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Figure 1

 (A, B) Serum ghrelin and tumour necrosis factor α (TNF-α) levels in 27 patients with active ulcerative colitis (a-UC), 26 with ulcerative colitis in remission (r-UC), 15 with active Crohn’s disease (a-CD), 28 with Crohn’s disease in remission (r-CD), and 40 healthy controls. Data are mean (SD). (C) Correlation between serum ghrelin and TNF-α levels in patients with active inflammatory bowel disease.

Ghrelin values were abnormally high in active IBD patients (p<0.001 v controls and inactive IBD), with no significant differences between UC and CD patients (fig 1B), and normal in IBD patients in remission. There was a significant negative correlation between ghrelin and body mass index in normal subjects (r = −0.428, p<0.006) and IBD patients in remission (r = −0.464, p = 0.0004) whereas no correlation was found in active IBD (r = −0.161, NS). However, in active IBD patients, ghrelin correlated significantly with log transformed CRP (r = 0.425, p = 0.0051) and TNF-α levels (r = 0.712, p<0.0001) (fig 1C). Multiple regression analysis identified TNF-α as the only variable significantly associated with ghrelin in active IBD (p<0.0001), and body mass index in both the inactive IBD group (p = 0.002) and healthy subjects (p = 0.02).

This study demonstrates for the first time that high ghrelin levels, correlating positively with TNF-α, are a feature of active IBD and normalise in patients in remission. TNF-α is a proinflammatory cytokine with anorectic and catabolic properties.^2,10 A positive correlation between ghrelin and TNF-α levels has previously been found in cachectic states.^1,10 However, our active IBD patients had normal body mass index values, and their TNF-α pattern would be consistent with its role as mediator of intestinal inflammation.

In agreement with previously reported data,^2–7 our findings in IBD could suggest a possible role for endogenous ghrelin in the control of the inflammatory process. Moreover, in IBD, some inflammatory mediators and/or products could play a role in stimulating ghrelin release from gastrointestinal or extraintestinal tissues, such as immune cells, which are activated in the disease.^1,2

In conclusion, endogenous ghrelin secretion increases in active IBD although the real pathophysiological significance of its upregulation and the mechanisms involved remain unclear.