Fibroblast-Like Synovial Cells in Rheumatoid Arthritis--the Impact of Infliximab on Hexosaminidase Activity

Adv Clin Exp Med. 2015 Sep-Oct;24(5):807-13. doi: 10.17219/acem/27302.

Abstract

Background: The effect of multiple infusions of infliximab (INF), a chimeric anti-tumor necrosis factor alpha antibody, on the concentration of hexosaminidase (HEX) activity in a synovial cell culture derived from human synovial inflamed fluid obtained from patients suffering from rheumatoid arthritis (RA) has been evaluated.

Objectives: The aim of this study was to prove INF efficacy in RA.

Material and methods: Inflamed synovial fluid was taken from RA patients (a study group) and patients who had undergone knee trauma within 7 days (a control group). The following solutions of infliximab were used: 40, 60 and 140 µg/mL. Determination of the concentration of HEX activity in cell cultures was performed after 24, 48, 72 and 96 h of infliximab administration. To identify synoviocytes in cell culture immunohistochemical staining with vimentin and pancytokeratin was performed.

Results: A predominance of fibroblast-like synovial cells has been observed in the study group. In the control group the concentration of HEX activity without adding infliximab to the cell culture was 283.00 nkat/mL. After 96 h of incubation with infliximab, the concentrations of HEX activity in cultured synoviocytes according to infliximab doses of 40, 60 and 140 µg/mL were respectively: 280.00, 271.50 and 293.50 nkat/mL. In the study group, the concentration of HEX activity without adding infliximab to the cell culture was 542.27 nkat/mL. The final concentrations of HEX activity of cultured fibroblast-like synovial cells measured after 96 h of incubation with infliximab were: 471.72, 498.27 and 556.72 nkat/mL, according to infliximab doses of 40, 60 and 140 µg/mL. In all groups (besides the infliximab concentration of 140 µg/mL after 96 h of incubation), the level of concentration of HEX activity was significantly higher in the study group compared to the control group, irrespective of infliximab concentration and time of infliximab incubation.

Conclusions: Infliximab changes the concentration of HEX activity depending on the drug dose and time of administration.

MeSH terms

  • Adult
  • Antirheumatic Agents / pharmacology
  • Arthritis, Rheumatoid / enzymology
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Assays
  • Female
  • Fibroblasts / drug effects*
  • Fibroblasts / enzymology
  • Fibroblasts / metabolism
  • Hexosaminidases / metabolism*
  • Humans
  • Immunohistochemistry
  • Infliximab / pharmacology*
  • Keratins / metabolism
  • Male
  • Middle Aged
  • Synovial Fluid / cytology
  • Synovial Fluid / drug effects*
  • Time Factors
  • Vimentin / metabolism

Substances

  • Antirheumatic Agents
  • Vimentin
  • Keratins
  • Infliximab
  • Hexosaminidases