Abstract

PurposeInterleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC).MethodsConsecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls.ResultsIL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (> 5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance.ConclusionsOnly a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.

Highlights

  • The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in inflammatory diseases and inflammatory carcinogenesis

  • A significantly increased IL-6 production was reported in stimulated monocytes from patients with active inflammatory bowel disease (IBD) in comparison with samples from inactive disease phases or healthy control individuals [5, 6]

  • Our study provides comprehensive data on the suitability and limitations of IL-6, soluble IL-6R (sIL-6R) and sgp130 as potential biomarkers in IBD

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Summary

Introduction

The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in inflammatory diseases and inflammatory carcinogenesis. Strategies for its inhibition have gained increasing interest due to the success of the anti-interleukin-6 receptor (IL-6R) antibody tocilizumab in rheumatologic diseases [1,2,3,4]. A significantly increased IL-6 production was reported in stimulated monocytes from patients with active inflammatory bowel disease (IBD) in comparison with samples from inactive disease phases or healthy control individuals [5, 6]. A general increase of IL-6 in patients with IBD and animal models has been reported in several studies [7,8,9,10,11,12,13]. IL-6 binds to the specific cell membrane IL-6R expressed only on certain cell types, mainly leukocytes and hepatocytes, and the

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