Interrelated reduction of chemerin and plasminogen activator inhibitor-1 serum levels in rheumatoid arthritis after interleukin-6 receptor blockade

Clin Rheumatol. 2015 Mar;34(3):419-27. doi: 10.1007/s10067-014-2704-1. Epub 2014 Jun 10.


Inflammatory/metabolic factors and imbalance of haemostasis contribute to cardiovascular disease risk in rheumatoid arthritis (RA). Interleukin-6 (IL-6), a cytokine that plays an important role in immune responses, is implicated in its pathogenesis. In this study, the effects of the IL-6 receptor inhibitor, tocilizumab, on serum adipokines and coagulation/fibrinolysis factors in RA patients were examined. Nineteen consecutive patients (18 women, aged 48 ± 9 years) received six monthly infusions of 8 mg/kg tocilizumab for moderate or severe RA. Disease activity/severity, as well as serum levels of chemerin apelin, plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), glucose, insulin and lipids were measured at baseline and at 1, 3 and 6 months thereafter. Chemerin and PAI-1 levels decreased significantly from baseline through 3 to 6 months (from 256 ± 79 to 174 ± 12 and 210 ± 85 ng/ml; from 73 ± 27 to 56 ± 22 and 51 ± 28 pg/ml, respectively). Other adipokines did not change, despite increases in adiposity. In multivariate models, significant independent associations were found between baseline chemerin with age, body mass index, remission of disease, HAQ-Di, CRP and PAI-1. Chemerin decrease at 6 months was significantly associated with PAI-1 and IL-6 changes at 6 months. Baseline PAI-1 associated negatively with remission of disease and total cholesterol, while PAI-1 change at 6 months associated with chemerin changes and smoking status. In conclusion, inhibition of IL-6 signaling in RA favorably alters chemerin and PAI-1 levels in an interrelated manner, despite increasing adiposity. This might represent a dual anti-inflammatory and anti-thrombotic/fibrinolytic mechanism of tocilizumab that may reduce cardiovascular event risk in RA patients.

MeSH terms

  • Adipokines / blood
  • Adult
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Chemokines / blood*
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Interleukin-6 / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Plasminogen Activator Inhibitor 1 / blood*


  • Adipokines
  • Antibodies, Monoclonal, Humanized
  • Chemokines
  • IL6 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-6
  • Plasminogen Activator Inhibitor 1
  • RARRES2 protein, human
  • SERPINE1 protein, human
  • tocilizumab