Role of Interleukin- (IL-) 17 in the Pathogenesis and Targeted Therapies in Spondyloarthropathies

Chyuan, I‐Tsu; Chen, Ji-Yih

doi:10.1155/2018/2403935

Cited by 37 publications

(19 citation statements)

References 101 publications

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“…However, it is known that up to 40% of patients do not benefit from TNF-α blockade due to loss of efficacy or drug tolerance issues [14][15][16]. Therefore, the need to find alternative treatments for these patients has led to the development of further drugs able to block another pivotal cytokine involved in axSpA inflammation, such as interleukin-(IL-) 17 [17]. The human anti-IL-17A monoclonal antibody secukinumab (SCK) has been approved for the treatment of ankylosing spondylitis (AS), after proving its effectiveness in 5 multicentre phase III trials, including 4 randomized double blind trials and their extensions (MEASURE 1 [18], MEASURE 2 [18], MEASURE 3 [19], MEASURE 4 [20], and MEASURE 2-J [21]).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Effectiveness of Secukinumab in Patients with Axial Spondyloarthritis

Gentileschi

Rigante

Sota

et al. 2020

Mediators of Inflammation

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Objectives. The primary aim of our study was to evaluate long-term efficacy of secukinumab (SCK) in patients with axial spondyloarthritis (axSpA); secondary aims were to evaluate drug retention rate and to identify differences in the clinical and laboratory assessment according to axSpA clinical features, dosage administered, and biologic treatment lines. Patients and Methods. We collected clinical, demographical, and treatment data from 39 patients affected by axSpA consecutively treated with SCK. Laboratory assessment was based on inflammation parameters; clinical assessment was performed with the Ankylosing Spondylitis Disease Activity Score- (ASDAS-) CRP and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Data were recorded at baseline and every 3 months for the first year and then every 6 months in the second year. Results. Twelve males and 27 females were enrolled; both BASDAI and ASDAS-CRP showed a statistically significant reduction during the observation period (p<0.0001 and p<0.0001, respectively). C-reactive protein significantly decreased (p=0.006), with significant reduction at the post hoc analysis between baseline and both 6-month evaluation (p=0.02) and 24-month visit (p=0.036). No statistical significance was observed in BASDAI and ASDAS-CRP improvement (p=0.482 and p=0.164, respectively) between different dosages administered. No significant differences emerged in the BASDAI and ASDAS-CRP variations between biologic-naïve patients and subjects previously failing to tumour necrosis factor (TNF) inhibitors (p=0.53 and p=0.148, respectively). At the end of our observation, 7 out of 39 patients discontinued SCK. The global retention rate at the end of the study period was 78.2%, without any significant differences between biologic-naïve and anti-TNF-failure patients (p=0.619) or between subjects administered with different SCK dosages (p=0.614). No adverse events were reported. Conclusions. In our cohort, SCK has proved a remarkable effectiveness regardless biologic treatment line and dosages employed. As suggested by the notable drug retention rate, SCK has been able to maintain its effectiveness over a considerable long period of treatment.

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Section: Introductionmentioning

confidence: 99%

Long-Term Effectiveness of Secukinumab in Patients with Axial Spondyloarthritis

Gentileschi

Rigante

Sota

et al. 2020

Mediators of Inflammation

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“…В отношении регуляции воспалительного процесса ЦК разделяют на провоспалительные (инициирующие и усиливающие воспалительную реакцию) и противовоспалительные (подавляющие воспаление). К основным провоспалительным ЦК, принимающим участие в патогенезе воспалительных заболеваний суставов, относятся интерлейкины IL-1β, IL-6, IL-8, IL-17, а также фактор некроза опухоли альфа (TNFα) и интерферон гамма (IFNγ) [3,19,53].…”

Section: цитокины при ювенильных артритахunclassified

Сoncentration of Anti-Inflamatory Cytokines in Cell Culture Supernatants in Children With Juvenile Idiopathic Arthritis

2019

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Juvenile idiopathic arthritis is a chronic inflammatory disease of the joints in children, mainly of autoimmune or auto-inflammatory nature. It is a heterogeneous group, which includes different subtypes of the disease. Different mechanisms may play role in the pathogenesis of distinct subtypes of juvenile arthritis. However, a long-term imbalance of pro- and anti-inflammatory cytokines is important for all subtypes of disease. The aim of the present study was to determine spontaneous and stimulated anti-inflammatory cytokines production by peripheral blood cells from the children with juvenile idiopathic arthritis. Patients of 2 to 17 years old with different subtypes of juvenile idiopathic arthritis (n = 99) and healthy children without signs of autoimmune diseases (control, n = 31) were examined. Spontaneous and phytohemagglutinin-stimulated concentrations of IL-1ra, IL-4, IL-10, TGF-β in supernatants of whole-blood cultures were determined by ELISA. Differences in the spontaneous and mitogen-stimulated secretion of the cytokines in patients with different subtypes of juvenile arthritis have not been revealed. The spontaneous IL-1ra, IL-4 and IL-10 production by blood cells in the common group of patients with juvenile idiopathic arthritis was similar to the controls. The median value of spontaneous TGF-β concentration in the patients was below the detection level, whereas blood cells of healthy children had a higher potential of spontaneous TGF-β production. IL-4 and IL-10 production after incubation of peripheral blood cells with phytohemagglutinin in patients and in the control group did not differ from the controls, while IL-1ra and TGF-β synthesis was significantly lower than in healthy children.The spontaneous and/or stimulated production of IL-1ra, TGF-β by blood cells in children with juvenile idiopathic arthritis reflects the pathogenic significance of these cytokines in disease. Stimulation of cells can reveal a latent deficiency in the synthesis of cytokines, which is not evident when determining its concentration in serum or supernatants of spontaneous whole-blood cultures.

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“…As a result, IL-17 mediates angiogenesis, recruitment of inflammatory cells, and induction of proinflammatory mediator release [16]. IL-17 receptor is expressed in vivo in chondrocytes from different arthropathies (RA, OA, and seronegative spondyloarthropathies) [20], and IL-17 is implicated in multiple joint pathologies, such as psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis [21,22], and drugs targeting IL-17 have been approved for treatment of psoriatic arthritis [23]. In OA patients, elevated serum and synovial fluid levels of IL-17 were reported to show a positive correlation with radiographic features of the disease [24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the interleukin-17 effect on articular cartilage in a translational model: an explorative study

Sinkevičiūtė

Aspberg

et al. 2020

BMC Rheumatol

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Background: Osteoarthritis (OA) is a progressive, chronic disease characterized by articular cartilage destruction. The pro-inflammatory cytokine IL-17 levels have been reported elevated in serum and synovial fluid of OA patients and correlated with increased cartilage defects and bone remodeling. The aim of this study was to characterize an IL-17-mediated articular cartilage degradation ex-vivo model and to investigate IL-17 effect on cartilage extracellular matrix protein turnover. Methods: Full-depth bovine femoral condyle articular cartilage explants were cultured in serum-free medium for three weeks in the absence, or presence of cytokines: IL-17A (100 ng/ml or 25 ng/ml), or 10 ng OSM combined with 20 ng/ml TNFα (O + T). RNA isolation and PCR analysis were performed on tissue lysates to confirm IL-17 receptor expression. GAG and ECM-turnover biomarker release into conditioned media was assessed with dimethyl methylene blue and ELISA assays, respectively. Gelatin zymography was used for matrix metalloproteinase (MMP) 2 and MMP9 activity assessment in conditioned media, and shotgun LC-MS/MS for identification and label-free quantification of proteins and protein fragments in conditioned media. Western blotting was used to validate MS results. Results: IL-17RA mRNA was expressed in bovine full-depth articular cartilage and the treatment with IL-17A did not interfere with metabolic activity of the model. IL-17A induced cartilage breakdown; conditioned media GAG levels were 3.6-fold-elevated compared to untreated. IL-17A [100 ng/ml] induced ADAMTS-mediated aggrecan degradation fragment release (14-fold increase compared to untreated) and MMP-mediated type II collagen fragment release (6-fold-change compared to untreated). MS data analysis revealed 16 differentially expressed proteins in IL-17A conditioned media compared to untreated, and CHI3L1 upregulation in conditioned media in response to IL-17 was confirmed by Western blotting. Conclusions: We showed that IL-17A has cartilage modulating potential. It induces collagen and aggrecan degradation indicating an upregulation of MMPs. This was confirmed by zymography and mass spectrometry data. We also showed that the expression of other cytokines is induced by IL-17A, which provide further insight to the pathways that are active in response to IL-17A. This exploratory study confirms that IL-17A may play a role in cartilage pathology and that the applied model may be a good tool to further investigate it.

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Role of Interleukin- (IL-) 17 in the Pathogenesis and Targeted Therapies in Spondyloarthropathies

Cited by 37 publications

References 101 publications

Long-Term Effectiveness of Secukinumab in Patients with Axial Spondyloarthritis

Long-Term Effectiveness of Secukinumab in Patients with Axial Spondyloarthritis

Сoncentration of Anti-Inflamatory Cytokines in Cell Culture Supernatants in Children With Juvenile Idiopathic Arthritis

Characterization of the interleukin-17 effect on articular cartilage in a translational model: an explorative study

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