Fasciola hepatica extract suppresses fibroblast-like synoviocytes in vitro and alleviates experimental arthritis

Abstract

Background: Rheumatoid arthritis (RA) is a chronic infammatory disease characterized by synovial infammation, fbroblast-like synoviocytes (FLS) activation and joint destruction. Fasciola hepatica is a platyhelminth that releases excretory-secretory immunomodulatory products capable of suppressing the Th1 immune response. Despite the efectiveness of available treatments for inducing disease remission, current options are not successful in all patients and may cause side efects. Thus, we evaluated the therapeutic potential of F. hepatica extract on FLS from RA patients and arthritis models. Methods: FLS were isolated from synovial fuid of RA patients, cultured, and exposed to F. hepatica extract (60, 80, and 100 µg/ml) for diferent time points to assess cell viability, adherence, migration and invasion. For in vivo experi ments, mice with antigen (AIA) and collagen (CIA) induced arthritis received a 200 µg/dose of F. hepatica extract daily. Statistical analysis was performed by ANOVA and Student’s t-test using GraphPad Prism 6.0. Results: In vitro assays showed that extract decreased FLS cell viability at concentration of 100 µg/ml (83.8%±5.0 extract vs. 100.0%±0.0 control; p<0.05), adherence in 20% (92.0 cells±5.8 extract vs. 116.3 cells±7.9 control; p<0.05), migratory potential (69.5%±17.6 extract vs. 100.0% control; p<0.05), and cell invasiveness potential through the matrigel (76.0%±8.4 extract vs. 100.0% control; p<0.01). The extract reduced leukocyte migration by 56% (40× 104 leukocytes/knee±19.00) compared to control (90.90× 104 leukocytes/knee±12.90) (p<0.01) and nocic eption (6.37 g±0.99 extract vs. 3.81 g±1.44 control; p<0.001) in AIA and delayed clinical onset of CIA (11.75±2.96 extract vs. 14.00±2.56 control; p=0.126). Conclusion: Our results point out a potential immunomodulatory efect of F. hepatica extract in RA models. There fore, the characterization of promising new immunomodulatory molecules should be pursued, as they can promote the development of new therapies