The insulin-like growth factor (IGF) system and its relation to infliximab treatment in adult patients with Crohn's disease.
OBJECTIVE
Metabolic bone disease (MBD) and muscle wasting (MW) are serious complications in adult patients suffering from inflammatory bowel disease. These complications may be caused by alterations in the insulin-like growth factor (IGF) system. The aim of the present study was to assess changes in the IGF system in patients with active Crohn's disease (CD) before and during infliximab treatment.


METHODS
We studied 13 patients with therapy refractory CD, treated with infliximab (5 mg/kg body-weight) at baseline and after 2 weeks. The IGF system and markers of inflammation were examined at baseline, on days 2-5 and after 1, 4, and 8 weeks. Ten healthy age- and gender-matched persons served as controls.


RESULTS
Total IGF-I and IGF binding protein (IGFBP)-3 levels were reduced by 36% (p<0.05) and 27% (p<0.001), respectively, compared with those of controls, and normalized during the study period. Free IGF-I levels were reduced by 46% (p<0.05) compared with those of controls and remained suppressed. IGFBP-2 levels were increased at baseline by a factor 2.3 compared to controls (p<0.01) with partial normalization at the end of the study period. The Crohn's disease Activity Index, the Harvey Bradshaw Index, C-reactive protein, orosomucoid and albumin reached normal levels during infliximab treatment.


CONCLUSIONS
Treatment with infliximab normalized circulating levels of total IGF-I and IGFBP-3, and partially normalized IGFBP-2, whereas free IGF-I remained suppressed. We suggest that the changes in the IGF system may be part of the catabolic state in active CD and may have an association with MBD and MW.
Eivindson
Martin
M
Hepatological-Gastroenterological Department V, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark. DocMartin@dadlnet.dk
Grønbaek
Henning
H
Skogstrand
Kristin
K
Thorsen
Poul
P
Frystyk
Jan
J
Flyvbjerg
Allan
A
Dahlerup
Jens F
JF
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy; D016207:Cytokines / Q000097:blood; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D000069285:Infliximab; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D009961:Orosomucoid / Q000032:analysis; D012709:Serum Albumin / Q000032:analysis
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D016207:Cytokines; D005765:Gastrointestinal Agents; D018836:Inflammation Mediators; D018970:Insulin-Like Growth Factor Binding Protein 1; D009961:Orosomucoid; D012709:Serum Albumin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D002097:C-Reactive Protein; D000069285:Infliximab