A novel inhibitory pathway of synovial inflammation exerted by glucocorticoids and tumour necrosis factor inhibitors via lymphocyte activation gene-3 up-regulation: an ex vivo study
Authors' conclusion
This study proposes a novel regulatory mechanism of GCs and of TNF inhibitors mediated by LAG-3 up-regulation in synovial cells and PBMCs.
Study context
- Population
- Synovial fluid mononuclear cells (SFMCs) from psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, synovial fluid cells (SFCs) from osteoarthritis (OA) patients and PBMCs of healthy donors
- Participants
- 26 / 13 / 5 / 14
- Comparison
- Glucocorticoids (GCs), RU486, methotrexate (MTX) and biologics vs medium in co-cultured synovial and peripheral cells
- PsAn = 26
- RAn = 13
- OAn = 5
- Healthy donorsn = 14
- Outcome
- LAG-3 and PD-1 expression on immune subsets (flow cytometry)
Methodological detailsex vivo, flow cytometry
- Ex vivo
- Flow cytometry
Main finding
As reported in the abstract
GCs vs medium: SFMC growth
2.3 (0.4) × 105vs 5.3 (0.7) × 105
P < 0.01
GCs vs medium: CD14+LAG-3+ cells
11.7 (2.4)% vs 0.8 (0.3)%
P < 0.0001
MTX: no effect on CD14+LAG-3+ cells
0.7 (0.3)%
Infliximab (IFX) and etanercept vs medium: CD14+LAG-3+ cells (not IL-12/23 inhibitor)
2.0 (0.6)% and 1.6 (0.4)% vs 0.5 (0.1)%
P < 0.03
Further findings
Correlation of GC SFMC growth inhibition with CD14+LAG-3+ up-regulation (PsA and RA)
- R
- 0.53, P = 0.03
RU486 vs GC alone: GC-induced CD14+LAG-3+ up-regulation
- 5 µM, 50 µM vs GC alone (dose-dependent inhibition)
- 5.3 (1.2)% and 1.3 (0.5)% vs 7.0 (1.4)%, P < 0.003
- RU486: no significant effect on CD14+LAG-3+ cells co-cultured with IFX
GCs in healthy donors' PBMCs
- Up-regulated CD3+LAG-3+, CD14+LAG-3+ and CD14+PD-1+ cells
Original publication
Composed by AI from the published abstract and checked against it. How Briefs are made →