Synovial monocytes from psoriatic and rheumatoid arthritis patients are modulated differently by TNF inhibitors and glucocorticoids: an ex-vivo study

S. Gertel, A. Polachek, V. Furer, D. Paran, R. Tzemach, D. Levartovsky, I. Litinsky, M. Anouk, K. Meridor, H. Nochomovitz, J. Wollman, M. Berman, S. Borok, O. Elkayam

Research output: Contribution to journalArticlepeer-review

Abstract

Synovial monocytes (expressing CD14+CD16+) affect pro-inflammatory responses in the synovium microenvironment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA). The effect of various drugs on those cells was evaluated. Methods Synovial fluid mononuclear cells (SFMCs) from PsA (n=29) and RA (n=11) patients were cultured with biologics or glucocorticoids (GCs). CD14+CD16+ cells were analysed by flow cytometry. TNF secretion was assessed by ELISA and changes in cytokine and matrix metalloproteinase-9 (MMP-9) mRNA by qPCR. Results TNF inhibitors (i) [adalimumab (ADA) and infliximab (IFX)] significantly reduced the %CD14+CD16+ cells (p<0.04 and p<0.02, respectively) compared to IL-17Ai, IL-12/23i, and GCs in PsA patients'SFMCs. Similarly, those TNFi reduced the %CD14+CD16+ cells (p<0.05 and p<0.02, respectively) compared to IL-6Ri, CD20i and GCs in RA patients'SFMCs. TNFi (ADA p<0.01, IFX p=0.0003), and GCs (p<0.05) reduced TNF levels in PsA patients SFMCs supernatants. IFX down-regulated IL-1β mRNA (p<0.005) while GCs betamethasone (BET) (p<0.01) and methylprednisolone acetate (MPA) (p<0.005) led to IL-1β up-regulation. IFX down-regulated IL-8 and MMP-9 (p<0.01) and up-regulated IL-10 (p<0.005), and GCs did so to a greater extent (for IL-8, BET p<0.0001 and MPA p<0.005, for MMP-9, BET and MPA p<0.0001 and for IL-10, BET and MPA p<0.0001). Conclusion TNFi but not GCs reduced the inflammatory monocytes. Both TNFi and GCs inhibited TNF secretion but differently modulated IL-1β, IL-8, MMP-9 and IL-10 gene expression. Our data point to TNFi as a modulator of synovial monocytes.

Original languageEnglish
Pages (from-to)1847-1855
Number of pages9
JournalClinical and Experimental Rheumatology
Volume41
Issue number9
DOIs
StatePublished - Sep 2023

Keywords

  • glucocorticoids
  • monocytes
  • psoriatic arthritis
  • synovial fluid
  • tumour necrosis factor inhibitors

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