Interleukin-6 blockade with Tocilizumab decreases metalloproteinase-9 activity in synovial fibroblasts stimulated with synovial fluids of patients with Rheumatoid Arthritis or Spondyloarthritis

BLAS R; TAMSHIRO H; MUNARRIZ A; PARDO HIDALGO R; DI GENARO MS

Madrid

Congreso; Annual European Congress of Rheumatology EULAR 2017; 2017

Asociacion Europea de Reumatologia

Background:Fibroblast-like synoviocytes (FLS) exhibit a transformed aggressive phenotype characterized by increased secretion of pro-inflammatory cytokines and matrix metalloproteinases (MMPs). Early pathological mechanisms that explain the change to an altered phenotype in (FLS) of chronic inflammatory arthropathies remain largely unknown. The composition of synovial fluids (SF) is very complex and strongly influences the microenvironment of joints including FLS thus representing an inseparable element of the disease. The MMP-9 is a gelatinase expressed in three major forms: dimer, monomer and a complex with neutrophil gelatin-associated lipocalin (NGAL). Interleukin-(IL)-6 is a pleiotropic cytokine expressed by a variety of immune and non-immune cells. However, the mechanisms by which IL-6 contributes to the pathogenesis of chronic arthropathies are not fully understood.Objectives:The purpose of the present work was to perform a comparative study of the IL-6 production and MMP-9 activity of FLS stimulated with SF from patients with osteoarthritis (OA), rheumatoid arthritis (RA) or spondyloarthritis (SpA). In addition, the effect of IL-6 blockade on MMP-9 activity was evaluated.Methods:Primary FLS were obtained from SF of the RA patients. Furthermore, the human synovial SW982cell line was used. The SFof patients with OA (n=11), RA (n=11) or SpA (n=9)patients were pooled. The FLS were stimulated withOA, RA or SpASF poolsand supernatantswere collected after 24, 48 and 72 h. The IL-6 levels wereassessed in the SNby ELISA. The gelatinase activity of the cells culture supernatants was determined by zymography. The IL-6 function was blocked withthe anti-IL-6 receptor antagonist tocilizumab (TCZ) (40g/ml).Results: Earlier induction of IL-6 in FLSor SW982 cell line was observedby RA and SpA SF stimulation since significant levels were detected at 24h(p