Resveratrol, a phytochemical, acts several cellular signaling pathways and has anti‐inflammatory potentials. The purpose of this study is to research the therapeutic effect of resveratrol in collagen‐induced arthritis (CIA) model in rats and whether resveratrol affects the activities of signaling pathways those are potent pathogenic actors of rheumatoid arthritis. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant in Wistar albino rats. One day after the onset of arthritis (day 14), resveratrol (20 mg/kg/day) was given via oral gavage, until day 29. The paws of the rats were obtained for further analysis. Tissue Wnt5a, mitogen‐activated protein kinase (MAPK), Src tyrosine kinase and signal transducer, and activator of transcription‐3 (STAT3) mRNA expressions were determined by real‐time polymerase chain reaction. Resveratrol ameliorated the clinical and histopathological (perisynovial inflammation and cartilage‐bone destruction) findings of inflammatory arthritis. The tissue mRNA expressions of Wnt5a, MAPK3, Src kinase, and STAT3 were increased in the sham group compared to the control group. Resveratrol supplement decreased their expressions. The present study shows that Src kinase, STAT3, and Wnt signaling pathway are active in the CIA model. Resveratrol inhibits these signaling pathways and ameliorates inflammatory arthritis. © 2018 BioFactors, 45(1):69–74, 2019

Although the pathogenesis of systemic sclerosis is not exactly known, it is thought that immune activation has prominent roles in pathogenesis. Secukinumab is a monoclonal antibody against interleukin (IL)‐17A. Metformin, a widely used antidiabetic medication, has anti‐proliferative, immunomodulating and anti‐fibrotic activities. The purpose of our study is to determine the therapeutic efficacy of secukinumab and metformin on bleomycin (BLM) induced dermal fibrosis. Fifty Balb/c female mice were divided into 5 groups: (group 1 control, 2 sham, 3 secukinumab, 4 metformin and 5 secukinumab + metformin). The mice in the control group received 100 μL phosphate‐buffered saline (PBS), while the mice in other groups received 100 μL (100 μg) BLM in PBS subcutaneously (sc) every day for 4 weeks. In addition, mice in groups 3 and 5 received secukinumab at a dose of 10 mg/kg/wk sc, and mice in the groups 4 and 5 received oral metformin 50 mg/kg/d for 28 days. All groups of mice were sacrificed at the end of the 4th week and tissue samples were taken for analysis. In addition to histopathological analysis, skin tissue messenger RNA (mRNA) expressions of IL‐17 and collagen 3A were measured by real‐time polymerase chain reaction. Repeated BLM injections had caused dermal fibrosis. In addition, the mRNA expressions of IL‐17 and collagen 3A were increased in the BLM group. Secukinumab and metformin ameliorated dermal fibrosis. They decreased dermal thickness and tissue IL‐17A and collagen 3A mRNA levels. Secukinumab and metformin exhibit anti‐fibrotic effects in the BLM‐induced dermal fibrosis.

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The aim of the European Journal of Rheumatology is to cover various aspects of rheumatology for its readers, encompassing the spectrum of diseases with arthritis, musculoskeletal conditions, autoinflammatory diseases, connective tissue disorders, osteoporosis, translational research, the latest therapies and treatment programs. European Journal of Rheumatology publishes original articles, invited reviews, case based reviews, letters to the editor and images in rheumatology. The publication language of the journal is English.

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Background/aim: Sjögren's syndrome (SS) is an autoimmune disease and its pathogenesis is still not completely clear. The Wingless (Wnt) / β -catenin pathway has recently been shown to play an important role in inflammation. This study aims to determine the serum and saliva levels of Dickkopf (DKK)1 and sclerostin and evaluate Wnt-1 and Wnt-3a expression in the salivary gland in patients with primary SS. Materials and methods:This study included 30 patients diagnosed with SS, 30 patients diagnosed with systemic lupus erythematosus (SLE), and 29 healthy controls. Serum and saliva levels of DKK1 and sclerostin were measured and the expressions of Wnt1 and Wnt3a in the salivary gland were measured immunohistochemically.Results: Serum DKK1 and sclerostin levels were lower in the SS and SLE groups compared to the control group (both p < 0.001). Saliva DKK1 levels were higher in the SS group compared to the control and SLE groups (p = 0.004 and p = 0.009, respectively). Wnt1 and Wnt3a expression were found in salivary gland tissue samples in 71.4% of primary SS patients and relatively frequent than control group. Conclusions: Serum DKK1 and sclerostin levels in primary SS and SLE were decreased. Moreover, levels of Wnt1 and Wnt3a expression in the salivary gland were also elevated in primary SS. Therefore, it can be concluded that the Wnt / β -catenin pathway activities may be altered in case of glandular inflammation.

Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is important in the process of inflammation and fibrosis. The adenosine 5′-monophosphate-activated protein kinase (AMPK) enzyme can affect JAK/STAT pathway. Tofacitinib is a pan-JAK inhibitör. Metformin activates AMPK enzyme. We aimed to investigate the therapeutic efficacy of tofacitinib and metformin on IL-17 and TGF-β cytokines, skin fibrosis and inflammation in mouse model of systemic sclerosis (SSc). 40 Balb/c female mice were divided into 4 groups: (control, sham (BLM), tofacitinib and metformin). The mice in the tofacitinib group received oral tofacitinib (20 mg/kg/daily) and mice in the metformin group received oral metformin (50 mg/kg/day) for 28 days. At the end of 4th week, all groups of mice were decapitated and tissue samples were taken for analysis. Histopathological analysis of skin tissue was performed, and mRNA expressions of collagen 3A, IL-17 and TGF-β were assessed by real-time PCR and ELISA. Repeated BLM injections had induced dermal fibrosis. Moreover, the tissue levels of collagen 3A, IL-17 and TGF-β were elevated in the BLM group. Tofacitinib and metformin mitigated dermal fibrosis. They reduced dermal thickness and tissue collagen 3A, IL-17 and TGF-β levels. Tofacitinib and metformin demonstrated anti-inflammatory and anti-fibrotic effects in the mouse model of SSc.

BackgroundTURKBIO registry is the Turkish version of Danish DANBIO rheumatologic database which has been established in 2011. Demographics and previous or current treatment with conventional (csDMARD) and targeted synthetic (tsDMARD), and biological DMARDs (bDMARDs) were collected.ObjectivesWe aimed to investigate the efficacy and safety status of methotrexate (MTX) vs. leflunomide (LEF) use as a concomitant treatment with bDMARDs and tsDMARD in this registry.MethodsFrequencies of achievement of remission or remission +low disease activity (LDA) at the 6th month of bDMARD or tsDMARD treatment were compared between patients who were on these medications with MTX vs. LEF as a concomitant treatment. Drug survival and switch rates of bDMARDs and tsDMARD treatments either with MTX or LEF were compared. The adverse effects with MTX and LEF concomitant use were evaluated as well.ResultsThe study included 725 bDMARD or tsDMARD receiving RA patients from 8 participating centres of the TURKBIO registry. Of these patients, 462 (63.7%) were receiving concomitant MTX and 263 (36.3%) LEF. Demographic findings are given in the table 1. Achievement of remission and remission +LDA at the 6th month of bDMARD or tsDMARD initiation was similar in concomitant MTX vs LEF groups (51.4% vs. 53%, p=0.683). When each bDMARD and tsDMARD was evaluated separately, achievement of remission were again similar in MTX and LEF concomitant users (TNFi: 53% vs. 54%; ABA: 50% vs. 59%; RTX: 53% vs. 61%; TCZ: 42% vs. 35%; p>0.05 for all). For TOFA, although remission +LDA rate was numerically higher in MTX concomitant group than LEF group (42% vs. 21%), the difference was not statistically significant due to the smaller sample size of TOFA (n=33). The results were similar for all DMARD groups when remission was evaluated alone. Drug survival (17±12 vs. 16±11 months, p>0.05) and drug discontinuation (42,2 vs 38, p>0.05) rates of bDMARDs or tsDMARD were also not different in MTX vs. LEF concomitant users. Adverse effects rate (19.5% vs 20.5%, p>0.05) were similar between MTX vs. LEF concomitant users as well.Abstract FRI0134 – Table 1Demographic findings of patients.ConclusionsAchievement of remission or remission +LDA was not different with the concomitant use of MTX vs. LEF with any bDMARD or tsDMARD treatment in RA patients with a similar safety profile. LEF might be an alternative as a concomitant DMARD in MTX-intolerant RA patients initiating bDMARDs or tsDMARD.Disclosure of InterestNone declared