title: Interrelated reduction of chemerin and plasminogen activator inhibitor-1 serum levels in rheumatoid arthritis after interleukin-6 receptor blockade.
abstract: 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.
authors.affiliation: First Department of Propaedeutic/Internal Medicine, University of Athens Medical School, Laiko General Hospital, 17 Ag. Thoma St., 11527, Athens, Greece, kmakrila@med.uoa.gr.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Makrilakis
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Fragiadaki
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Smith
authors.forename: Petros P
authors.initials: PP
authors.lastname: Sfikakis
authors.forename: George D
authors.initials: GD
authors.lastname: Kitas
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D018925:Chemokines / Q000097:blood*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D000093242:Interleukin-6 Inhibitors; D015850:Interleukin-6
chemical_list: D054392:Adipokines; D061067:Antibodies, Monoclonal, Humanized; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D017395:Plasminogen Activator Inhibitor 1; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; D015850:Interleukin-6; C478630:RARRES2 protein, human; C051321:SERPINE1 protein, human; C502936:tocilizumab