TABLE 3.
Main studies investigating the relationships between TNF-α- and IL-23/IL-17A-driven proinflammatory pathways in psoriatic synovitis.
| Study | Type of study | Laboratory technique | Main results |
|---|---|---|---|
| Fiocco et al. (2010) | Longitudinal SF analysis before and at the last time SF sample was available for aspiration after IA-ETA treatment. | Luminex analysis | Longitudinal decreases in IL-1b, IL-6, and IL-22 levels in the SF AND no variation in IL-17A. |
| Noordenbos et al. (2012) | Longitudinal ST analysis before and after 12 weeks of systemic ETA treatment. | Double immunofluorescence | Longitudinal decrease in IL-positive cells AND no variation in IL-17-positive mast cells. |
| Mens et al. (2018) | Longitudinal ST analysis before and after 12 weeks of systemic SEC treatment. | Quantitative RT-PCR | Longitudinal reductions in IL-17A, IL-6, CCL-20, and MMP-3 mRNA levels AND no variations in IL-8 or TNF-α levels. |
| Chen et al. (2019) | Longitudinal ST analysis before and after 12 weeks of systemic SEC treatment. | IHC | Longitudinal reduction in IL-17A-positive non-mast cells AND increase in IL-17A-positive mast cells. |
| Raychaudhuri et al. (2012) | In vitro study, FLSs treated with IL-17A, TNF-α, and an IL-17RA blocker. | ELISA | TNF-α and IL-17A in vitro similarly increase IL-6, IL-8, and MMP-3 production in FLS cultures, while the IL-17RA blocker reduces the production. |
| Mitra et al. (2012) | In vitro study, FLSs treated with IL-22 and TNF-α. | Proliferation assays (MTT and CFSE dilution assays). | IL-22 and TNF-α-induced FLS proliferation AND IL-22 + TNF-α had a synergistic effect on FLS proliferation. |
| Gao et al. (2016) | In vitro study, synovial explant cultures treated with tofacitinib or DMSO. | ELISA | Ample effect of tofacitinib on in vitro cytokine production, reducing IL-8, IL-6, MCP-1, and MMP-3. IL-17A not detectable; TNF-α not evaluated. |
| Raychaudhuri et al. (2017) | In vitro study, SFMCs treated with tofacitinib. | FACS | Tofacitinib reduced IL-23-induced CD4 + CD11a + CD45RO + IL-17 + T cells. |
| Frommer et al. (2019) | In vitro study, FLSs treated with IL-17A, TNF-α, SEC, and ADA. | ELISA | IL-17A increases IL-6 release into FLS culture supernatants; TNF-α had a synergistic effect on increasing IL-6 release AND SEC and ADA had similar effects on IL-6 release inhibition. |
| Xu et al. (2020) | In vitro study, SFMC, and FLS coculture with SEC or ADA. | ELISA | SEC reduced IL-17A, IL-8 and IL-6 release; ADA reduced IL-8, TNF-α, and MMP-3/13. |
| Wade et al. (2019) | In vitro study, synovial cell suspensions treated in vitro with the PDE4 inhibitor rolipram. | ST single-cell suspension analysis + FACS. | Cells triple positive for GM-CSF, TNF-α, and IL-17 or IFN-γ were enriched in the PsA synovium compared to the peripheral blood and correlated with disease activity AND they were reduced by in vitro administration of rolipram. |
| Steel et al. (2020) | Cross-sectional study. | FACS | IL-17-positive CD8 T cells triple positive for GM-CSF, TNF-α, and IFN-γ, were enriched in the SF compared with the peripheral blood. |
TNF-α, tumor necrosis factor-alpha; IL, interleukin; SF, synovial fluid; IA, intra-articular; ETA, etanercept; ST, synovial tissue; SEC, secukinumab; RT-PCR, real-time polymerase chain reaction; mRNA, messenger RNA; IHC, immunohistochemistry; FLS, fibroblast-like synoviocyte; IL-17RA, interleukin 17 receptor A; ELISA, enzyme-linked immunosorbent assay; MMP, matrix metalloproteinase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; CFSE, carboxy fluorescein succinimidyl ester; DMSO, dimethylsulfoxide; MCP-1, monocyte chemoattractant protein-1; SFMCs, synovial fluid mononuclear cells; FACS, Hi-D fluorescence-activated cell sorting; ADA, adalimumab; PDE4, phosphodiesterase-4; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon.