Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFα inhibitors

Clin Rheumatol. 2010 Nov;29(11):1301-9. doi: 10.1007/s10067-010-1528-x. Epub 2010 Jul 18.


The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated with tumor necrosis factor-alpha (TNFα) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n=32, and psoriatic arthritis, n=17) initiating TNFα inhibitor therapy (infliximab, n=38; etanercept, n=8; and adalimumab, n=3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6-12 weeks for up to 3 years. Patients with co-morbidities (n=4), missing baseline samples (n=3), and adverse events (n=5) were excluded. Patients with SpA had compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98-64) vs. 1.3 (0.33-26)), VEGF (105 ng/l (22-752) vs. 45 (12-351)), YKL-40 (74 μg/l (14-572) vs. 43 (20-184)), and MMP-3 (43 μg/l (9.1-401) vs. 16 (2.5-47), p≤0.001), whereas total aggrecan was lower (662 μg/l (223-2,219) vs. 816 (399-2,190), p≤0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p≤0.03) in clinical responders (n=24), and persistent reductions over 3 years were found in IL-6, VEGF, YKL-40, and MMP-3. Only MMP-3 decreased (p≤0.02) in non-responders (n=13). The study demonstrated changes of plasma IL-6, VEGF, YKL-40, MMP-3, and total aggrecan and a potential value for monitoring disease activity and treatment response in SpA patients. Larger prospective studies are required to clarify clinical utility of these biomarkers.

MeSH terms

  • Adipokines
  • Adult
  • Aged
  • Aggrecans / biosynthesis*
  • Biomarkers / metabolism
  • Chitinase-3-Like Protein 1
  • Cohort Studies
  • Female
  • Gene Expression Regulation*
  • Glycoproteins / blood*
  • Humans
  • Interleukin-6 / blood*
  • Interleukin-6 / metabolism
  • Lectins / blood*
  • Male
  • Matrix Metalloproteinase 3 / blood*
  • Middle Aged
  • Spondylarthritis / metabolism*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / blood*
  • Vascular Endothelial Growth Factor A / metabolism


  • Adipokines
  • Aggrecans
  • Biomarkers
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • Interleukin-6
  • Lectins
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 3