AB0089 IN VITRO EFFECT OF FASCIOLA HEPATICA EXTRACT ON SYNOVIAL FIBROBLAST OF RHEUMATOID ARTHRITIS PATIENTS
Authors: Suelen Dalmolin, Renata Ternus Pedo, Mirian Farinon, Jordana Miranda de Souza Silva, Vanessa Hax, Martin Cancela, Henrique Bunselmeyer Ferreira, Rafaela Cavalheiro Do Espírito Santo, Fabiany Gonçalves, Ricardo Xavier
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Synovial fibroblasts (FLS) have an aggressive and invasive profile and play a major role in RA[1]. Available therapeutic options are effective for induction and maintenance of disease remission[2], but not all patients respond to treatment and there is no cure. So new therapeutic options need to be explored. Studies have shown that products secreted by helminths contain components with anti-inflammatory properties[3 4], capable of suppressing Th1 immune response[5] and the production of inflammatory cytokines[6]. One example is the immunomodulating properties[7] of the extract of <i>Fasciola hepatica</i>. <h3>Objectives:</h3> To evaluate the effects of <i>F. hepatica</i> extract in FLS from RA patients. <h3>Methods:</h3> Firstly, the cultures of FLS collected from the synovial fluid of RA patients were exposed at different concentration of <i>F. hepatica</i> extract (60μg/mL, 80μg/mL and 100μg/mL) and analyzed after 24h, 48h and 72h by MTT cell proliferation assay. FLS controls were exposed to standard culture medium. The effect of extract was also evaluated through adhesion and wound healing assay, and TNF-α production after IFN<i>g</i> stimulation. Statistical analysis was performed with ANOVA or T Test and the <i>p</i>&lt;0.05 were considered statistically significant. <h3>Results:</h3> <i>F. hepatica</i> extract decreased the cell proliferation of FLS at concentration of 100μg/ml after 48h (83.8% ± 5.0 extract <i>vs</i> 100.0% ± 0.0 control; <i>p</i>&lt;0.05), and at concentrations of 80 μg/ml (88.4% ± 3.0 extract <i>vs</i> 100.0% ± 0.0 control; <i>p</i>&lt;0.05) and 100 μg/ml (89.8% extract ± 3.8 extract <i>vs</i> 100.0% ± 0.0 control; <i>p</i>&lt;0. 05) after 72h, when compared with control group. Based on these results, the concentration of 100μg/ml and the time of 48h were chosen for the following tests. The treatment with extract showed a decreased of FLS adhesion (92.0 cells ± 5.8 extract <i>vs</i> 116.3 cells ± 7.9 control; <i>p</i>&lt;0.05) and migratory potential (40.2 inch/h ± 13.9 extract <i>vs</i> 58.7 inch/h ± 6.5 control). Moreover, after treatment there was a trend of decreased TNF levels (7.0 pg/mL ± 0.5 extract <i>vs</i> 8.1 pg/mL ± 0.7 control). <h3>Conclusion:</h3> Taken together, our results suggest that extract of <i>F. hepatica</i> is able to reduce the aggressive and invasive profile of FLS. However, further analyses are needed for a better understanding the mechanisms of the effect of <i>F. hepatica</i> extract on FLS and its different components, such as cystatin. <h3>References</h3> [1] Bottini N, et al. Nat Rev Rheumatol. 2013;9(1):24–33. [2] Tanaka Y. Korean J Intern Med. 2016;31(2): 210–218. [3] Hamilton C, et al. Infect. Immun. 2009;(77):2488–98. [4] Wang S, et al. Parasites &amp; Vetors. 2016;(9):6. [5] Donnelly S. Infection and immunity. 2005;(73):166–73. [6] Ravidà A, et al. Molecular &amp; cellular proteomics: MCP. 2016;15(3139–3153). [7] Cancela M, et al. Parasitology. 2017;144(13):1695–707. <h3>Acknowledgement:</h3> FIPE/HCPA, Serviço de Reumatologia/HCPA <h3>Disclosure of Interests:</h3> Suelen Dalmolin: None declared, Renata Ternus Pedo: None declared, Mirian Farinon: None declared, Jordana Miranda de Souza Silva: None declared, Vanessa Hax: None declared, Martin Cancela: None declared, Henrique Bunselmeyer Ferreira: None declared, Rafaela Cavalheiro do Espírito Santo: None declared, Fabiany Gonçalves: None declared, Ricardo Xavier Consultant for: Abbvie, Pfizer, Novartis, Janssen, Lilly, Roche