Increased plasma ghrelin following infliximab in Crohn's disease.
BACKGROUND
Ghrelin, a potent orexigenic peptide produced by the stomach, may be affected by circulating inflammatory mediators.


OBJECTIVE
To assess the effect of an anti-TNFα antibody on ghrelin in patients with Crohn's disease (CD).


METHODS
Fifteen patients with Crohn's receiving infliximab were studied before and 1 week after infusion. Following an overnight fast, blood was sampled before a meal and then every 20 min for 2 h. Total ghrelin and CRP were measured using ELISA. Acylated ghrelin and TNFα, IFNγ, IL-1β and IL-6 were measured with bioplex. Harvey Bradshaw Activity Index was assessed.


RESULTS
Median (95% CI) 2-h integrated plasma total ghrelin increased from 162 (99-311) before infliximab to 200 (128-387) pg/mL h, (P = 0.02) after. Following infliximab, 20 min postmeal, median acylated ghrelin decreased from 50.3 (24-64) to 38.6 (26-82) pg/mL, (P = 0.04) thus reverting to a traditional meal related ghrelin curve. Median (range) disease activity decreased from 5 (2-28) before to 3 (0-22), (P = 0.0001) and Median (95% CI) TNFα decreased from 2.8 (1.89-4.48) to 1.31 (0.73-2.06) pg/mL (P = 0.002).


CONCLUSIONS
Infliximab increases circulating total ghrelin by 25% in CD and restores the postprandial response of acylated ghrelin to food intake. Acylated and de-sacyl ghrelin remain unchanged, suggesting that an alternate isoform could be affected by infliximab.
Sung
E Z H
EZ
University Hospital, Coventry Unit for Diabetes and Metabolism, University of Warwick, Coventry Neurology (Harlow, UK) and Immunoinflammatory Centre of Excellence in Drug Discovery, GlaxoSmithKline, Stevenage, UK.
Da Silva
N F
NF
Goodyear
S
S
McTernan
P G
PG
Sanger
G J
GJ
Nwokolo
C U
CU
D000328:Adult; D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005765:Gastrointestinal Agents / Q000097:blood / Q000627:therapeutic use*; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000627:therapeutic use*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D054439:Ghrelin; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab