Evidence for continuous stimulation of interleukin-6 production in Crohn's disease.
Increased serum concentrations of acute-phase proteins can be found in active inflammatory bowel disease. Because interleukin 6 (IL-6) is one of the main mediators of acute-phase protein synthesis by the liver, the serum concentrations of IL-6 and the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and alpha 1-acid glycoprotein were determined in 70 patients with Crohn's disease (CD) and 23 patients with ulcerative colitis (UC). Disease activities were determined by established clinical activity indices. Serum IL-6 concentrations were significantly (P less than 0.005) increased in patients with CD (mean +/- SEM, 6.8 +/- 0.9 U/mL) compared with patients with UC (mean, less than 4 U/mL) and healthy controls (mean, less than 4 U/mL). Of patients with CD, 68.5% had serum IL-6 concentrations of greater than or equal to 4 U/mL, compared with 21.7% of patients with UC and 0% of healthy controls. There was a tendency toward higher serum IL-6 concentrations in patients with active CD than in patients with inactive disease. However, these differences were not statistically significant. There was no correlation between IL-6 serum concentrations and clinical activity indices, possibly because of the short circulatory lifetime and rapid hepatic clearance of IL-6 from the portal venous blood. In contrast to serum IL-6, acute-phase proteins, which have a longer circulatory lifetime, were significantly correlated with clinical activity indices. Only the follow-up of individual patients with initially highly active disease showed a further increase in IL-6 levels during acute exacerbations of the inflammatory process. The results show that most patients with even moderately active CD have significantly increased serum concentrations of IL-6, most probably reflecting a continuous stimulation of IL-6-producing cells.
Gross
V
V
Department of Internal Medicine, University of Freiburg, Germany.
Andus
T
T
Caesar
I
I
Roth
M
M
Schölmerich
J
J
D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000096:biosynthesis; D003093:Colitis, Ulcerative / Q000097:blood; D003424:Crohn Disease / Q000097:blood*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000096:biosynthesis; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D009961:Orosomucoid; D000515:alpha 1-Antitrypsin; D002097:C-Reactive Protein