Artikel
Analysis of potential differential adipokine and IL-17 effects on synovial fibroblasts from different rheumatic disease backgrounds
Suche in Medline nach
Autoren
Veröffentlicht: | 5. Februar 2019 |
---|
Gliederung
Text
Background: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are similar but yet distinct diseases. RA and PsA synovial fibroblasts (SF), known key effector cells in the pathophysiology of chronic inflammatory arthritis, respond to various stimuli including adipokines and cytokines. We hypothesized that this may contribute to the differences between these diseases. For example, IL-17 (found in synovial tissue) has been a major therapeutic target in PsA but has not been equally effective in RA. Therefore, we evaluated the responses of SF from patients with PsA, RA or no rheumatic disease to IL-17 ± TNF-α and the adipokines visfatin and resistin, which show strong expression in the synovium of chronic inflammatory arthritis.
Methods: SF were isolated from patients with PsA, RA or non-rheumatic disease controls (N). PsASF, RASF and NSF were stimulated with recombinant IL-17A/F, TNF-α, visfatin, and resistin, while a neutralizing anti-IL-17A antibody was used to block IL-17A effects. Secretion of the proinflammatory cytokine IL-6 was quantified using an immunoassay.
Results: Although visfatin caused a strong increase in IL-6 secretion in all SF types (n=3 each), differences in response were not statistically significant between the SF types studied. No effect was observed with resistin. IL-17A at concentrations found in serum or synovial fluid did not induce IL-6 secretion in any of the SF. Dose-response curve analysis showed that considerably higher concentrations of IL 17A are required for the induction of IL-6 secretion. An anti-IL 17A antibody abolished the effect, thus showing that the effect is specific for IL-17A. The effects of IL-17A and IL 17F on IL-6 secretion by PsASF could be strongly amplified by a co-stimulation with TNF-α (IL-17A: 5-fold ↑ vs 113-fold ↑; IL-17F: 1.7-fold ↑ vs 39-fold ↑; TNF-α alone: 12-fold ↑). The effects were stronger for IL-17A than for IL 17F with or without TNF co-stimulation.
Conclusion: SF from RA and PsA patients were not differentially affected by the adipokines visfatin and resistin or IL-17A when used at serum or synovial fluid concentrations suggesting inflammatory cells to be the primary target of anti-IL-17 therapy.
Acknowledgements: This work was supported by an unrestricted educational grant from Celgene GmbH.